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In this study, we utilize high-resolution electron microscopy alongside machine learning and physics-based simulations to investigate how such clot microstructure impacts molecular diffusivity. We used Serial Block Face \u2013 Scanning Electron Microscopy (SBF-SEM) to image select volumes of hemostatic masses formed in a mouse jugular vein, producing high-resolution 2D images. Images were segmented using machine learning software (Cellpose), whose training was augmented by manually segmented images. The segmented images were then utilized as 2D computational domains for Lattice Kinetic Monte-Carlo (LKMC) simulations. This process constitutes a computational pipeline that combines purely data-derived biological domains with physics-driven simulations to estimate how molecular movement is hindered in a hemostatic platelet mass. Using our pipeline, we estimated that the 2D hindered diffusion rates of a globular protein range from 2% to 40% of the unhindered rate, with denser packing regions lending to lower molecular diffusivity. These data suggest that coagulation reactions rates, thrombin generation and activity, as well as platelet releasate activity may be drastically impacted by the internal geometry of a hemostatic thrombus.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012853","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T14:20:26Z","timestamp":1751898026000},"page":"e1012853","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["From imaging to computational domains for physics-driven molecular biology simulations: Hindered diffusion in platelet masses"],"prefix":"10.1371","volume":"21","author":[{"given":"Catherine","family":"House","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3916-0035","authenticated-orcid":true,"given":"Ziyi","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3989-6399","authenticated-orcid":true,"given":"Kaushik N.","family":"Shankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra J.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan E.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L.","family":"Diamond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Tomaiuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Stalker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2489-1613","authenticated-orcid":true,"given":"Talid","family":"Sinno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"issue":"6","key":"pcbi.1012853.ref001","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1007\/s10439-013-0764-z","article-title":"Simulation of intrathrombus fluid and solute transport using in vivo clot structures with single platelet resolution","volume":"41","author":"RS Voronov","year":"2013","journal-title":"Ann Biomed Eng"},{"issue":"11","key":"pcbi.1012853.ref002","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1182\/blood-2014-01-550335","article-title":"A systems approach to hemostasis: 1. 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