Multiwell Combinatorial Hydrogel Array for High-Throughput Analysis of Cell-ECM Interactions.

Autor: Lei R; Department of Chemistry, Latimer Hall, University of California, Berkeley, Berkeley, California 94720, United States.; Department of Bioengineering, Stanley Hall, University of California, Berkeley, Berkeley, California 94720, United States., Akins EA; Department of Bioengineering, Stanley Hall, University of California, Berkeley, Berkeley, California 94720, United States.; University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Stanley Hall, Berkeley, California 94720, United States., Wong KCY; Department of Bioengineering, Stanley Hall, University of California, Berkeley, Berkeley, California 94720, United States., Repina NA; Department of Bioengineering, Stanley Hall, University of California, Berkeley, Berkeley, California 94720, United States.; University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Stanley Hall, Berkeley, California 94720, United States., Wolf KJ; Department of Bioengineering, Stanley Hall, University of California, Berkeley, Berkeley, California 94720, United States.; University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Stanley Hall, Berkeley, California 94720, United States., Dempsey GE; Department of Nutritional Sciences and Toxicology, Morgan Hall, University of California, Berkeley, California 94720, United States., Schaffer DV; Department of Bioengineering, Stanley Hall, University of California, Berkeley, Berkeley, California 94720, United States.; University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Stanley Hall, Berkeley, California 94720, United States.; Department of Molecular and Cell Biology, Life Sciences Addition, University of California, Berkeley, California 94720, United States.; Department of Chemical and Biomolecular Engineering, Gilman Hall, University of California, Berkeley, Berkeley, California 94720, United States., Stahl A; University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Stanley Hall, Berkeley, California 94720, United States.; Department of Nutritional Sciences and Toxicology, Morgan Hall, University of California, Berkeley, California 94720, United States., Kumar S; Department of Bioengineering, Stanley Hall, University of California, Berkeley, Berkeley, California 94720, United States.; University of California, Berkeley - University of California, San Francisco Graduate Program in Bioengineering, Stanley Hall, Berkeley, California 94720, United States.; Department of Chemical and Biomolecular Engineering, Gilman Hall, University of California, Berkeley, Berkeley, California 94720, United States.; Department of Bioengineering and Therapeutic Sciences, Byers Hall, University of California, San Francisco, San Francisco, California 94143, United States.
Jazyk: angličtina
Zdroj: ACS biomaterials science & engineering [ACS Biomater Sci Eng] 2021 Jun 14; Vol. 7 (6), pp. 2453-2465. Date of Electronic Publication: 2021 May 24.
DOI: 10.1021/acsbiomaterials.1c00065
Abstrakt: Biophysical cues in the extracellular matrix (ECM) regulate cell behavior in a complex, nonlinear, and interdependent manner. To quantify these important regulatory relationships and gain a comprehensive understanding of mechanotransduction, there is a need for high-throughput matrix platforms that enable parallel culture and analysis of cells in various matrix conditions. Here we describe a multiwell hyaluronic acid (HA) platform in which cells are cultured on combinatorial arrays of hydrogels spanning a range of elasticities and adhesivities. Our strategy utilizes orthogonal photopatterning of stiffness and adhesivity gradients, with the stiffness gradient implemented by a programmable light illumination system. The resulting platform allows individual treatment and analysis of each matrix environment while eliminating contributions of haptotaxis and durotaxis. In human mesenchymal stem cells, our platform recapitulates expected relationships between matrix stiffness, adhesivity, and cell mechanosensing. We further applied the platform to show that as integrin ligand density falls, cell adhesion and migration depend more strongly on CD44-mediated interactions with the HA backbone. We anticipate that our system could bear great value for mechanistic discovery and screening where matrix mechanics and adhesivity are expected to influence phenotype.
Databáze: MEDLINE
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