{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T10:04:00Z","timestamp":1789553040781,"version":"build-2803163510"},"reference-count":116,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Micromachines"],"abstract":"<jats:p>The biological microenvironment is inherently mechanical, with cells continuously sensing and responding to fluid shear stress, matrix stiffness, tensile strain, hydrostatic pressure, and other physical cues through highly conserved mechanotransduction pathways. These mechanical interactions arise across biological interfaces and are increasingly investigated using microfluidic and nanofluidic technologies that enable precise control of physiologically relevant mechanical environments. While nanomedicine has traditionally focused on biochemical targeting and molecular recognition, growing evidence demonstrates that interfacial mechanical forces critically regulate nanoparticle transport, vascular adhesion, cellular uptake, biodistribution, therapeutic activation, and treatment efficacy. Simultaneously, pathological alterations in tissue mechanics have emerged as hallmarks of numerous diseases, including cancer, cardiovascular disease, fibrosis, pulmonary hypertension, neurodegeneration, and metabolic disorders, creating new opportunities for mechanics-guided therapeutic design. This Perspective develops an integrative framework in which interfacial mechanics is treated as an actionable engineering variable across the nanotherapeutic delivery pathway. The framework distinguishes three mechanistic roles of mechanics: as a determinant of therapeutic transport, as an activation signal for mechanically responsive materials, and as a biological target through mechanotransduction pathways. Particular attention is given to fluid shear stress, extracellular-matrix mechanics, strain, pressure, nano\u2013cell interfacial interactions, and the use of microfluidic and nanofluidic systems to reproduce physiologically relevant mechanical environments. Experimentally demonstrated mechanically responsive systems are distinguished from prospective concepts, and the translational implications of mechanical heterogeneity, activation thresholds, off-target triggering, and combined mechanical\u2013biochemical gating are examined. The Perspective further identifies quantitative and experimental requirements needed to advance mechanics-guided nanotherapeutics from conceptual designs toward predictive and clinically translatable systems. Collectively, this framework positions interfacial mechanics as a complementary design dimension to molecular targeting in precision drug delivery.<\/jats:p>","DOI":"10.3390\/mi17091086","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:06:37Z","timestamp":1789549597000},"page":"1086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering Nanotherapeutics Through Interfacial Mechanics: Mechanobiology and Precision Drug Delivery"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2031-9057","authenticated-orcid":false,"given":"Alireza","family":"Mohammad Karim","sequence":"first","affiliation":[{"name":"Ingram School of Engineering, Texas State University, San Marcos, TX 78666, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1021\/nn900002m","article-title":"Impact of nanotechnology on drug delivery","volume":"3","author":"Farokhzad","year":"2009","journal-title":"ACS Nano"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1038\/nnano.2007.387","article-title":"Nanocarriers as an emerging platform for cancer therapy","volume":"2","author":"Peer","year":"2007","journal-title":"Nat. Nanotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrc.2016.108","article-title":"Cancer nanomedicine: Progress, challenges and opportunities","volume":"17","author":"Shi","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/ncpcardio1397","article-title":"Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology","volume":"6","author":"Davies","year":"2009","journal-title":"Nat. Clin. Pract. Cardiovasc. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jconrel.2011.06.001","article-title":"Targeted drug delivery to tumors: Myths, reality and possibility","volume":"153","author":"Bae","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles of nanoparticle design for overcoming biological barriers to drug delivery","volume":"33","author":"Blanco","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/nmat3776","article-title":"Stimuli-responsive nanocarriers for drug delivery","volume":"12","author":"Mura","year":"2013","journal-title":"Nat. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3790","DOI":"10.1529\/biophysj.107.120238","article-title":"The receptor-mediated endocytosis of nonspherical particles","volume":"94","author":"Decuzzi","year":"2008","journal-title":"Biophys. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/j.nano.2015.07.015","article-title":"Design considerations for nanotherapeutics in oncology","volume":"11","author":"Stylianopoulos","year":"2015","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-bioeng-071811-150124","article-title":"The effect of nanoparticle size, shape, and surface chemistry on biological systems","volume":"14","author":"Albanese","year":"2012","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.biomaterials.2007.09.025","article-title":"Design maps for nanoparticles targeting the diseased microvasculature","volume":"29","author":"Decuzzi","year":"2008","journal-title":"Biomaterials"},{"key":"ref_13","first-page":"3039","article-title":"Transport of molecules in the tumor interstitium: A review","volume":"47","author":"Jain","year":"1987","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/nrc1456","article-title":"High interstitial fluid pressure\u2014An obstacle in cancer therapy","volume":"4","author":"Heldin","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.trecan.2018.02.005","article-title":"Reengineering the Physical Microenvironment of Tumors to Improve Drug Delivery and Efficacy: From Mathematical Modeling to Bench to Bedside","volume":"4","author":"Stylianopoulos","year":"2018","journal-title":"Trends Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1146\/annurev-biochem-081820-092427","article-title":"Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis","volume":"90","author":"Sorkin","year":"2021","journal-title":"Annu. Rev. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eaaz0868","DOI":"10.1126\/science.aaz0868","article-title":"Physical traits of cancer","volume":"370","author":"Nia","year":"2020","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/nature08908","article-title":"Cell mechanics and the cytoskeleton","volume":"463","author":"Fletcher","year":"2010","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nrm3667","article-title":"Functions and mechanics of dynein motor proteins","volume":"14","author":"Roberts","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrm2216","article-title":"Pathways of clathrin-independent endocytosis","volume":"8","author":"Mayor","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1080\/07853890310016333","article-title":"Mechanobiology and diseases of mechanotransduction","volume":"35","author":"Ingber","year":"2003","journal-title":"Ann. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrm1890","article-title":"Local force and geometry sensing regulate cell functions","volume":"7","author":"Vogel","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1126\/science.1116995","article-title":"Tissue cells feel and respond to the stiffness of their substrate","volume":"310","author":"Discher","year":"2005","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/nrm2597","article-title":"Mechanotransduction gone awry","volume":"10","author":"Jaalouk","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Martino, F., Perestrelo, A.R., Vinarsky, V., Pagliari, S., and Forte, G. (2018). Cellular Mechanotransduction: From Tension to Function. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00824"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.1193270","article-title":"Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels","volume":"330","author":"Coste","year":"2010","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrm.2017.92","article-title":"Piezos thrive under pressure: Mechanically activated ion channels in health and disease","volume":"18","author":"Murthy","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.neuron.2015.08.032","article-title":"Mechanically Activated Ion Channels","volume":"87","author":"Ranade","year":"2015","journal-title":"Neuron"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.cell.2009.10.027","article-title":"Matrix crosslinking forces tumor progression by enhancing integrin signaling","volume":"139","author":"Levental","year":"2009","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1083\/jcb.201004082","article-title":"Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression","volume":"190","author":"Liu","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.bbadis.2013.02.007","article-title":"Tissue mechanics and fibrosis","volume":"1832","author":"Wells","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrc2544","article-title":"A tense situation: Forcing tumour progression","volume":"9","author":"Butcher","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1152\/physrev.00047.2009","article-title":"Effects of disturbed flow on vascular endothelium: Pathophysiological basis and clinical perspectives","volume":"91","author":"Chiu","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nrm2596","article-title":"Mechanotransduction in vascular physiology and atherogenesis","volume":"10","author":"Hahn","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/nrm3896","article-title":"Mechanotransduction and extracellular matrix homeostasis","volume":"15","author":"Humphrey","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrm.2017.108","article-title":"Mechanical forces direct stem cell behaviour in development and regeneration","volume":"18","author":"Vining","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1083\/jcb.201609037","article-title":"Integrin-mediated mechanotransduction","volume":"215","author":"Sun","year":"2016","journal-title":"J. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrm2593","article-title":"Environmental sensing through focal adhesions","volume":"10","author":"Geiger","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/nrm.2017.87","article-title":"Mechanobiology of YAP and TAZ in physiology and disease","volume":"18","author":"Panciera","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1152\/physrev.1995.75.3.519","article-title":"Flow-mediated endothelial mechanotransduction","volume":"75","author":"Davies","year":"1995","journal-title":"Physiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"H1209","DOI":"10.1152\/ajpheart.01047.2006","article-title":"Mechanotransduction and endothelial cell homeostasis: The wisdom of the cell","volume":"292","author":"Chien","year":"2007","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1001\/jama.282.21.2035","article-title":"Hemodynamic shear stress and its role in atherosclerosis","volume":"282","author":"Malek","year":"1999","journal-title":"JAMA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1182\/blood-2002-01-0046","article-title":"Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2)","volume":"100","author":"Dekker","year":"2002","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1172\/JCI24787","article-title":"Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2","volume":"116","author":"Parmar","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1073\/pnas.83.7.2114","article-title":"Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro","volume":"83","author":"Davies","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1172\/JCI111298","article-title":"Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells","volume":"73","author":"Davies","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1161\/01.ATV.5.3.293","article-title":"Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress","volume":"5","author":"Ku","year":"1985","journal-title":"Arteriosclerosis"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H1916","DOI":"10.1152\/ajpheart.00897.2003","article-title":"Spatial comparison between wall shear stress measures and porcine arterial endothelial permeability","volume":"286","author":"Himburg","year":"2004","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/cvr\/cvy004","article-title":"Dynamic and diverse changes in the functional properties of vascular smooth muscle cells in pulmonary hypertension","volume":"114","author":"Stenmark","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70598","DOI":"10.1002\/mco2.70598","article-title":"Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets","volume":"7","author":"Ren","year":"2026","journal-title":"MedComm"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1801887","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: State of the art and research perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur. Respir. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1016\/j.biomaterials.2007.02.013","article-title":"The role of specific and non-specific interactions in receptor-mediated endocytosis of nanoparticles","volume":"28","author":"Decuzzi","year":"2007","journal-title":"Biomaterials"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11901","DOI":"10.1073\/pnas.0705326104","article-title":"Making polymeric micro- and nanoparticles of complex shapes","volume":"104","author":"Champion","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"028104","DOI":"10.1103\/PhysRevLett.108.028104","article-title":"Margination of white blood cells in microcapillary flow","volume":"108","author":"Fedosov","year":"2012","journal-title":"Phys. Rev. Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15350","DOI":"10.1039\/C8NR04042G","article-title":"Influence of particle size and shape on their margination and wall-adhesion: Implications in drug delivery vehicle design across nano-to-micro scale","volume":"10","author":"Cooley","year":"2018","journal-title":"Nanoscale"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11095-008-9697-x","article-title":"Intravascular delivery of particulate systems: Does geometry really matter?","volume":"26","author":"Decuzzi","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1038\/srep02079","article-title":"On the near-wall accumulation of injectable particles in the microcirculation: Smaller is not better","volume":"3","author":"Lee","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.bpj.2013.12.020","article-title":"The wall-stress footprint of blood cells flowing in microvessels","volume":"106","author":"Freund","year":"2014","journal-title":"Biophys. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1549-8719.2010.00056.x","article-title":"Blood flow and cell-free layer in microvessels","volume":"17","author":"Fedosov","year":"2010","journal-title":"Microcirculation"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nnano.2007.70","article-title":"Shape effects of filaments versus spherical particles in flow and drug delivery","volume":"2","author":"Geng","year":"2007","journal-title":"Nat. Nanotechnol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.jconrel.2009.10.014","article-title":"Size and shape effects in the biodistribution of intravascularly injected particles","volume":"141","author":"Decuzzi","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_64","first-page":"261","article-title":"Statistics of cell adhesion under hydrodynamic flow: Simulation and experiment","volume":"19","author":"Hammer","year":"1993","journal-title":"Blood Cells"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.1016\/j.biomaterials.2006.05.024","article-title":"The adhesive strength of non-spherical particles mediated by specific interactions","volume":"27","author":"Decuzzi","year":"2006","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1146\/annurev.biophys.37.032807.125804","article-title":"Biophysics of catch bonds","volume":"37","author":"Thomas","year":"2008","journal-title":"Annu. Rev. Biophys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/nature01605","article-title":"Direct observation of catch bonds involving cell-adhesion molecules","volume":"423","author":"Marshall","year":"2003","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","article-title":"Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy","volume":"307","author":"Jain","year":"2005","journal-title":"Science"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1038\/ncb2307","article-title":"Actin dynamics counteract membrane tension during clathrin-mediated endocytosis","volume":"13","author":"Boulant","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/S0006-3495(96)79323-2","article-title":"Motor protein mechanics: A stochastic model with minimal mechanochemical coupling","volume":"71","author":"Duke","year":"1996","journal-title":"Biophys. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4466","DOI":"10.1038\/ncomms5466","article-title":"Poking cells for efficient vector-free intracellular delivery","volume":"5","author":"Wang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1021\/acsnano.2c07852","article-title":"High-Throughput and Efficient Intracellular Delivery Method via a Vibration-Assisted Nanoneedle\/Microfluidic Composite System","volume":"17","author":"Li","year":"2023","journal-title":"ACS Nano"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6644","DOI":"10.1021\/acsnano.5b03569","article-title":"Accelerating the Translation of Nanomaterials in Biomedicine","volume":"9","author":"Mitragotri","year":"2015","journal-title":"ACS Nano"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1126\/science.1217815","article-title":"Shear-activated nanotherapeutics for drug targeting to obstructed blood vessels","volume":"337","author":"Korin","year":"2012","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"15012","DOI":"10.1038\/natrevmats.2015.12","article-title":"The design of reversible hydrogels to capture extracellular matrix dynamics","volume":"1","author":"Rosales","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1161\/CIRCRESAHA.116.304937","article-title":"Mechanotransduction in cardiac hypertrophy and failure","volume":"116","author":"Lyon","year":"2015","journal-title":"Circ. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1126\/science.1070821","article-title":"Self-assembly at all scales","volume":"295","author":"Whitesides","year":"2002","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"16290","DOI":"10.1039\/D4NR02088J","article-title":"Mimicking the extracellular world: From natural to fully synthetic matrices utilizing supramolecular biomaterials","volume":"16","author":"Rijns","year":"2024","journal-title":"Nanoscale"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1126\/science.1205962","article-title":"Functional supramolecular polymers","volume":"335","author":"Aida","year":"2012","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1073\/pnas.072065599","article-title":"Toward complex matter: Supramolecular chemistry and self-organization","volume":"99","author":"Lehn","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Geng, W.C. (2026). Recent Advances in Supramolecular Chemistry. Molecules, 31.","DOI":"10.3390\/molecules31101556"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/bip.21328","article-title":"Self-assembly of peptide amphiphiles: From molecules to nanostructures to biomaterials","volume":"94","author":"Cui","year":"2010","journal-title":"Biopolymers"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.nantod.2016.02.004","article-title":"Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery","volume":"11","author":"Habibi","year":"2016","journal-title":"Nano Today"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/nbt874","article-title":"Fabrication of novel biomaterials through molecular self-assembly","volume":"21","author":"Zhang","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1039\/C1CC15551B","article-title":"Self-assembling peptide scaffolds for regenerative medicine","volume":"48","author":"Matson","year":"2012","journal-title":"Chem. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1126\/science.1173155","article-title":"Functional amyloids as natural storage of peptide hormones in pituitary secretory granules","volume":"325","author":"Maji","year":"2009","journal-title":"Science"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6546","DOI":"10.1002\/adma.201505961","article-title":"Amyloid Fibrils as Building Blocks for Natural and Artificial Functional Materials","volume":"28","author":"Knowles","year":"2016","journal-title":"Adv. Mater."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6195","DOI":"10.1039\/c2cs35264h","article-title":"Supramolecular polymeric hydrogels","volume":"41","author":"Appel","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_89","first-page":"5","article-title":"Drug delivery and targeting","volume":"392","author":"Langer","year":"1998","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1126\/science.1178250","article-title":"An analytical solution to the kinetics of breakable filament assembly","volume":"326","author":"Knowles","year":"2009","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1023\/A:1015929109894","article-title":"Stability of protein pharmaceuticals","volume":"6","author":"Manning","year":"1989","journal-title":"Pharm. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1007\/s11095-024-03726-x","article-title":"Stability of Protein Pharmaceuticals: Recent Advances","volume":"41","author":"Manning","year":"2024","journal-title":"Pharm. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s11095-009-0045-6","article-title":"Stability of protein pharmaceuticals: An update","volume":"27","author":"Manning","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1021\/acs.jmedchem.5b00726","article-title":"Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide","volume":"58","author":"Lau","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1126\/science.1150057","article-title":"Role of intermolecular forces in defining material properties of protein nanofibrils","volume":"318","author":"Knowles","year":"2007","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"9758","DOI":"10.1073\/pnas.1218402110","article-title":"Proliferation of amyloid-\u03b242 aggregates occurs through a secondary nucleation mechanism","volume":"110","author":"Cohen","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"24251","DOI":"10.1073\/pnas.2006684117","article-title":"Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors","volume":"117","author":"Michaels","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1096\/fj.05-5424rev","article-title":"Cellular mechanotransduction: Putting all the pieces together again","volume":"20","author":"Ingber","year":"2006","journal-title":"FASEB J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1021\/bm0505078","article-title":"Shear flow induces amyloid fibril formation","volume":"7","author":"Hill","year":"2006","journal-title":"Biomacromolecules"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1002\/bip.21646","article-title":"The effects of shear flow on protein structure and function","volume":"95","author":"Bekard","year":"2011","journal-title":"Biopolymers"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"34272","DOI":"10.1074\/jbc.M109.049809","article-title":"Fibril fragmentation enhances amyloid cytotoxicity","volume":"284","author":"Xue","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1146\/annurev.biochem.72.121801.161542","article-title":"Mechanical processes in biochemistry","volume":"73","author":"Bustamante","year":"2004","journal-title":"Annu. Rev. Biochem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nature13701","article-title":"Piezo1 integration of vascular architecture with physiological force","volume":"515","author":"Li","year":"2014","journal-title":"Nature"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"10347","DOI":"10.1073\/pnas.1409233111","article-title":"Piezo1, a mechanically activated ion channel, is required for vascular development in mice","volume":"111","author":"Ranade","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41467-017-00429-3","article-title":"Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance","volume":"8","author":"Rode","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1161\/ATVBAHA.119.313348","article-title":"Force sensing by Piezo channels in cardiovascular health and disease","volume":"39","author":"Beech","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.tibs.2021.01.008","article-title":"Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels","volume":"46","author":"Jiang","year":"2021","journal-title":"Trends Biochem. Sci."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1038\/nn.4162","article-title":"Piezo2 is the principal mechanotransduction channel for proprioception","volume":"18","author":"Woo","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nature13980","article-title":"Piezo2 is the major transducer of mechanical forces for touch sensation in mice","volume":"516","author":"Ranade","year":"2014","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ceb.2018.08.004","article-title":"Signal transduction via integrin adhesion complexes","volume":"56","author":"Humphries","year":"2019","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrc2748","article-title":"Integrins in cancer: Biological implications and therapeutic opportunities","volume":"10","author":"Desgrosellier","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2013.07.042","article-title":"A mechanical checkpoint controls multicellular growth through YAP\/TAZ regulation by actin-processing factors","volume":"154","author":"Aragona","year":"2013","journal-title":"Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nrc3876","article-title":"The emerging roles of YAP and TAZ in cancer","volume":"15","author":"Moroishi","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Noguchi, S., Saito, A., and Nagase, T. (2018). YAP\/TAZ Signaling as a Molecular Link between Fibrosis and Cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113674"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nrm2594","article-title":"Mechanotransduction at a distance: Mechanically coupling the extracellular matrix with the nucleus","volume":"10","author":"Wang","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41556-018-0038-y","article-title":"Emerging views of the nucleus as a cellular mechanosensor","volume":"20","author":"Kirby","year":"2018","journal-title":"Nat. Cell Biol."}],"container-title":["Micromachines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-666X\/17\/9\/1086\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:17:52Z","timestamp":1789550272000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-666X\/17\/9\/1086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":116,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["mi17091086"],"URL":"https:\/\/doi.org\/10.3390\/mi17091086","relation":{},"ISSN":["2072-666X"],"issn-type":[{"value":"2072-666X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}