{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:09:31Z","timestamp":1779365371198,"version":"3.53.0"},"posted":{"date-parts":[[2026,5,18]]},"group-title":"Biophysics","reference-count":108,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["R03EB034817"],"award-info":[{"award-number":["R03EB034817"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The protein corona (PC) that forms on the surface of nanomaterials upon contact with biological fluids provides a molecular snapshot of the host\u2019s physiological and pathological state. Here, we investigate two-dimensional (2D) titanium carbide (Ti\n                  <jats:sub>3<\/jats:sub>\n                  C\n                  <jats:sub>2<\/jats:sub>\n                  T\n                  <jats:italic>\n                    <jats:sub>x<\/jats:sub>\n                  <\/jats:italic>\n                  ) MXene nanosheets as nanobiointerfaces for capturing Alzheimer\u2019s disease (AD)\u2013associated plasma protein signatures. Ti\n                  <jats:sub>3<\/jats:sub>\n                  C\n                  <jats:sub>2<\/jats:sub>\n                  T\n                  <jats:italic>\n                    <jats:sub>x<\/jats:sub>\n                  <\/jats:italic>\n                  MXene flakes were incubated with plasma from clinically diagnosed AD patients and age-matched healthy controls (HC), leading to the formation of Ti\n                  <jats:sub>3<\/jats:sub>\n                  C\n                  <jats:sub>2<\/jats:sub>\n                  T\n                  <jats:italic>\n                    <jats:sub>x<\/jats:sub>\n                  <\/jats:italic>\n                  MXene\u2013PC complexes. Physicochemical characterization using dynamic light scattering, zeta potential analysis, and transmission electron microscopy revealed disease-dependent changes in hydrodynamic size, surface charge, and PC profile. Proteomic analysis of the isolated PC layers quantified 1,611 proteins without prior fractionation, demonstrating effective enrichment of low-abundance plasma components. Principal component analysis (PCA) revealed consistent separation between AD- and HC-derived Ti\n                  <jats:sub>3<\/jats:sub>\n                  C\n                  <jats:sub>2<\/jats:sub>\n                  T\n                  <jats:italic>\n                    <jats:sub>x<\/jats:sub>\n                  <\/jats:italic>\n                  MXene\u2013PC proteomes despite inter-individual heterogeneity. Differential abundance analysis identified selective enrichment of heterogeneous nuclear ribonucleoproteins (hnRNPs), annexins, and inflammatory mediators in AD-derived PC, implicating dysregulated RNA metabolism, membrane stress responses, and immune activation, hallmark processes in AD pathology. Our findings demonstrate that Ti\n                  <jats:sub>3<\/jats:sub>\n                  C\n                  <jats:sub>2<\/jats:sub>\n                  T\n                  <jats:italic>\n                    <jats:sub>x<\/jats:sub>\n                  <\/jats:italic>\n                  MXene\u2013PC interfaces act as selective molecular filters that reshape the detectable plasma proteome, enabling disease-associated molecular phenotyping and establishing a versatile nanointerface-driven framework for uncovering AD-related plasma signatures, providing a foundation for future translational diagnostic development.\n                <\/jats:p>","DOI":"10.64898\/2026.05.14.725150","type":"posted-content","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T16:45:16Z","timestamp":1779122716000},"source":"Crossref","is-referenced-by-count":0,"title":["MXene\u2013Protein Corona Interfaces for Molecular Profiling of Alzheimer\u2019s Disease"],"prefix":"10.64898","author":[{"given":"Samantha","family":"Velazquez","sequence":"first","affiliation":[{"name":"Department of Biology, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew C.","family":"Juber","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalton","family":"Brindley","sequence":"additional","affiliation":[{"name":"Department of Physics and Energy Science, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupma","family":"Thakur","sequence":"additional","affiliation":[{"name":"School of Materials Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Anasoori","sequence":"additional","affiliation":[{"name":"School of Materials Engineering, Purdue University, West Lafayette, IN 47907, USA"},{"name":"School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9083-5922","authenticated-orcid":false,"given":"Edward","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-6690","authenticated-orcid":false,"given":"Ali Akbar","family":"Ashkarran","sequence":"additional","affiliation":[{"name":"Department of Physics and Energy Science, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA"},{"name":"BioFrontiers Center, University of Colorado Colorado Springs, Colorado Springs, CO 80918, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052104401157000_2026.05.14.725150v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0332-9"},{"key":"2026052104401157000_2026.05.14.725150v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002"},{"key":"2026052104401157000_2026.05.14.725150v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0372-9"},{"issue":"4","key":"2026052104401157000_2026.05.14.725150v1.4","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3233\/JAD-2011-110458","article-title":"Review and meta-analysis of biomarkers and diagnostic imaging in Alzheimer\u2019s disease","volume":"26","year":"2011","journal-title":"Journal of Alzheimer\u2019s Disease"},{"issue":"1","key":"2026052104401157000_2026.05.14.725150v1.5","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3233\/JAD-2008-14103","article-title":"Identification of miRNA changes in Alzheimer\u2019s disease brain and CSF yields putative biomarkers and insights into disease pathways","volume":"14","year":"2008","journal-title":"Journal of Alzheimer\u2019s Disease"},{"key":"2026052104401157000_2026.05.14.725150v1.6","doi-asserted-by":"crossref","unstructured":"Hadoux, X. ; Hui, F. ; Lim, J. 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