{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:48:13Z","timestamp":1785739693459,"version":"3.56.0"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T00:00:00Z","timestamp":1785628800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Proteins are increasingly used to guide the crystallization of metal\u2013organic frameworks (MOFs), yielding protein@MOFs (p@MOFs) that encapsulate fragile biomacromolecules within stable crystalline hosts. These biohybrid materials offer tunable porosity and spatial organization that are difficult to achieve with conventional synthesis. Despite their growing importance, the mechanisms by which proteins influence MOF nucleation, crystal growth, and defect formation remain poorly understood. Here, we use a distributed electron microscopy approach to follow the full crystallization pathway of ferritin@ZIF\u20108 (Fn@ZIF\u20108). The method combines cryogenic transmission electron microscopy (cryo\u2010TEM), cryogenic electron tomography (cryo\u2010ET), and liquid\u2010phase TEM (LP\u2010TEM) to capture structural transitions over time. Using the ferritin iron oxide core as an intrinsic nanoscale tracer, we visualize the transformation of protein\u2010rich amorphous precursors into crystalline particles that ripen, aggregate, and develop large, surface\u2010accessible cavities. These cavities emerge only during later stages of growth, where localized dissolution and recrystallization restructure the framework. Concurrently, proteins become enriched near the crystal periphery and depleted from cavity\u2010rich regions. Our results suggest that protein organization and dissolution\u2010driven restructuring both contribute to defect formation. This work provides a mechanistic framework for understanding how hierarchical porosity develops in p@MOFs and establishes distributed electron microscopy as an approach for investigating biohybrid crystallization pathways.<\/jats:p>","DOI":"10.1002\/smll.74975","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T06:32:55Z","timestamp":1785738775000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cavity Formation in Protein@Metal\u2013Organic Frameworks Through Late\u2010Stage Crystal Dissolution"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8029-6048","authenticated-orcid":false,"given":"Rakia","family":"Dhaoui","sequence":"first","affiliation":[{"name":"Department of Chemistry University of California  Irvine California USA"},{"name":"Physical and Life Sciences Division Lawrence Livermore National Laboratory  Livermore California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin T.","family":"Mulvey","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Engineering University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmira","family":"Baghdadi","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovany G.","family":"Merham","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saira L.","family":"Cazares","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of California  Irvine California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1975-1854","authenticated-orcid":false,"given":"Joseph P.","family":"Patterson","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of California  Irvine California USA"},{"name":"Department of Materials Science and Engineering University of California  Irvine California 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