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Whether physiological breathing mechanics influence tumor cell extravasation is unknown. To address this, we developed a mechanically actuated microphysiological system combining perfusable lung-specific microvascular networks with breathing-like cyclic deformation. Under static conditions, lung-specific networks exhibited more lung-like vascular features and higher tumor cell extravasation rates than generic networks. The mechanically actuated device reproduced physiological tissue and vascular deformation, while 24 h of cyclic actuation did not alter vessel viability, permeability, or morphology compared with unactuated controls. Pre-actuation for 24 h, followed by tumor cell perfusion under static conditions, did not alter subsequent extravasation, whereas actuation initiated immediately after perfusion significantly increased extravasation compared with unactuated controls. This biomimetic platform enables direct investigation of how breathing-like vascular deformation influences metastasis and provides a versatile tool for studying vascular mechanobiology in the lung and other mechanically active organs.<\/jats:p>","DOI":"10.64898\/2026.09.17.752385","type":"posted-content","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T16:30:16Z","timestamp":1789749016000},"source":"Crossref","is-referenced-by-count":0,"title":["A mechanically actuated lung microvascular model reveals that breathing-like deformation enhances tumor cell extravasation"],"prefix":"10.64898","author":[{"given":"Marie A.","family":"Floryan","sequence":"first","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland M.","family":"Stoll","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar","family":"Fleps","sequence":"additional","affiliation":[{"name":"Independent researcher"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael N.","family":"Coates","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger D.","family":"Kamm","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"},{"name":"Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-5421","authenticated-orcid":false,"given":"Elena","family":"Cambria","sequence":"additional","affiliation":[{"name":"Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092212350600000_2026.09.17.752385v1.1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1979.47.5.990"},{"key":"2026092212350600000_2026.09.17.752385v1.2","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1152\/jappl.1987.62.4.1480","article-title":"Three-dimensional reconstruction of alveoli in the rat lung for pressure-volume relationships","volume":"62","year":"1987","journal-title":"Journal of Applied Physiology"},{"key":"2026092212350600000_2026.09.17.752385v1.3","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.86.6.2026"},{"key":"2026092212350600000_2026.09.17.752385v1.4","doi-asserted-by":"crossref","first-page":"L625","DOI":"10.1152\/ajplung.00105.2011","article-title":"What do we know about mechanical strain in lung alveoli?","volume":"301","year":"2011","journal-title":"Am J Physiol-Lung C"},{"key":"2026092212350600000_2026.09.17.752385v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-018-1747-9"},{"key":"2026092212350600000_2026.09.17.752385v1.6","first-page":"2023","article-title":"Acinar micromechanics in health and lung injury: what we have learned from quantitative morphology","volume":"14","year":"2023","journal-title":"Frontiers in Physiology"},{"key":"2026092212350600000_2026.09.17.752385v1.7","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.009817"},{"key":"2026092212350600000_2026.09.17.752385v1.8","doi-asserted-by":"crossref","unstructured":"Tian, Y.F. , Gawlak, G. , O\u2019Donnell, J.J. , Mambetsariev, I. , and Birukova, A.A . 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