biostudies-literatureUnknownJain KNIGMS NIH HHSUpon interaction with the extracellular matrix, the integrin receptors form nanoclusters as a first biochemical response to ligand binding. Here, we uncover a critical biodesign principle where these nanoclusters are spatially self-organized, facilitating effective mechanotransduction. Mouse Embryonic Fibroblasts (MEFs) with integrin β3 nanoclusters organized themselves with an intercluster distance of ~550 nm on uniformly coated fibronectin substrates, leading to larger focal adhesions. We determined that this spatial organization was driven by cell-intrinsic factors since there was no pre-existing pattern on the substrates. Altering this spatial organization using cyclo-RGD functionalized Titanium nanodiscs (of 100 nm, corroborating to the integrin nanocluster size) spaced at intervals obioRxiv : the preprint server for biology2023.11.20.567975https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690202biostudies-literatureIntrinsic self-organization of integrin nanoclusters within focal adhesions is required for cellular mechanotransduction.PMC10690202R01 GM113022Lim KYEChangede RJain KSheetz MPKanchanawong PfalseIntrinsic self-organization of integrin nanoclusters within focal adhesions is required for cellular mechanotransduction.Upon interaction with the extracellular matrix, the integrin receptors form nanoclusters as a first biochemical response to ligand binding. Here, we uncover a critical biodesign principle where these nanoclusters are spatially self-organized, facilitating effective mechanotransduction. Mouse Embryonic Fibroblasts (MEFs) with integrin β3 nanoclusters organized themselves with an intercluster distance of ~550 nm on uniformly coated fibronectin substrates, leading to larger focal adhesions. We determined that this spatial organization was driven by cell-intrinsic factors since there was no pre-existing pattern on the substrates. Altering this spatial organization using cyclo-RGD functionalized Titanium nanodiscs (of 100 nm, corroborating to the integrin nanocluster size) spaced at intervals o2023-01-01T00:00:00Z2023 Nov2025-04-25T17:16:38.598Z2025-04-25T17:16:38.598ZS-EPMC106902023804537810.1101/2023.11.20.567975