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In this study, we evaluated the cellular and molecular responses of freshwater algae (Chlamydomonas reinhardtii) following exposure to 100 nm silica-coated gold nanospheres (AuNPs) and nanostars (AuNSs) across multiple concentrations. Exposure to 10 mg\/L AuNSs for 72 h results in significantly stronger inhibition of algal growth and photosynthetic activity compared to the same concentration of AuNPs. Morphometric profiling reveals that AuNSs induce pronounced structural injury, including cell enlargement, debris production, and disruption of subcellular organization, more than AuNPs. Confocal imaging suggested that this heightened toxicity may stem from two distinct internalization patterns: AuNPs primarily adhered to chloroplast surfaces, whereas AuNSs caused more extensive membrane disruption and were observed deeper within intracellular compartments. RNA sequencing identified 9 upregulated and 38 downregulated differentially expressed genes (DEGs) in the 10 mg\/L AuNP-treated cells, impairing photosynthesis and energy storage via the photosystem II subunit S1 (PSBS1)\/early light-inducible protein (ELI3) pathway. In contrast, the AuNS group exhibits 246 upregulated and 145 downregulated DEGs, affecting membrane integrity and nitrogen metabolism through the nitrate reductase (NIT1)\/aminomethyl transferase (AMT1)\/protein kinase domain-containing protein (A0A2K3CRU5) pathway. These results demonstrate that the nanoparticle morphology can drive divergent toxicity mechanisms in algal cells. Our findings highlight the necessity of incorporating NP morphology into environmental risk assessments and suggest that safer nanomaterial design should consider shape-dependent interactions with aquatic microorganisms.<\/jats:p>","DOI":"10.1021\/envhealth.5c00839","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T21:26:23Z","timestamp":1784150783000},"page":"2416-2430","source":"Crossref","is-referenced-by-count":1,"title":["Shape-Dependent\nInteractions of Gold Nanoparticles\nwith Microalgae: Distinct Cellular and Molecular Responses"],"prefix":"10.1021","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6996-7017","authenticated-orcid":true,"given":"Can","family":"Wang","sequence":"first","affiliation":[{"name":"University of California Riverside , , , ,","place":["Riverside, California, United States, 92521"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8541-5333","authenticated-orcid":true,"given":"Bhaskar","family":"Sharma","sequence":"additional","affiliation":[{"name":"University of California Riverside , , , ,","place":["Riverside, California, United States, 92521"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1842-5465","authenticated-orcid":true,"given":"Ruonan","family":"Peng","sequence":"additional","affiliation":[{"name":"University of California Riverside , , , ,","place":["Riverside, California, United States, 92521"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8894-2750","authenticated-orcid":true,"given":"Xin","family":"Yong","sequence":"additional","affiliation":[{"name":"University at Buffalo , , , ,","place":["Buffalo, New York, United States, 14260"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis S.","family":"Santiago","sequence":"additional","affiliation":[{"name":"University of California Riverside , , , ,","place":["Riverside, California, United States, 92521"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6837-0927","authenticated-orcid":true,"given":"Ke","family":"Du","sequence":"additional","affiliation":[{"name":"University of California Riverside , , , ,","place":["Riverside, California, United States, 92521"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"issue":"5","key":"2026101607065761600_cit1","doi-asserted-by":"publisher","first-page":"2052","DOI":"10.3390\/ma16052052","article-title":"Properties,\nApplications and Toxicities of Organotrialkoxysilane-Derived Functional\nMetal Nanoparticles and Their Multimetallic Analogues","volume":"16","author":"Pandey","year":"2023","journal-title":"Materials (Basel)."},{"issue":"8","key":"2026101607065761600_cit2","doi-asserted-by":"publisher","first-page":"2633","DOI":"10.1039\/C6EE01092J","article-title":"TiO\/graphene\/NiFe-layered\ndouble\nhydroxide nanorod array photoanodes for efficient photoelectrochemical\nwater splitting","volume":"9","author":"Ning","year":"2016","journal-title":"Energ Environ. 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