How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.

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Cells interact with the extracellular matrix (ECM) through transmembrane adhesion receptors (integrins) that are linked to signalling proteins that regulate cell migration and ECM remodelling/synthesis. The cell-matrix adhesion complexes can vary in their molecular composition and in their function. Published data suggest that adapter proteins such as talin that couples integrins to actomyosin localise to force exerting focal adhesions (FA), whereas tensins mark a subset of adhesions called fibrillar adhesions (FB) that are linked to the remodelling of the cell ECM. FBs originate from FAs and here we aim to understand how molecular interactions lead to this transition.

Tensins bind to integrins and we have recently shown the association of two members of the tensin protein family (tensin1 and 3) with talin. Our pilot data suggest that talin contains multiple tensin binding sites and that they have an important role in the enrichment of tensins in FBs. Additional data show that the local enrichment of tensins leads to condensates through liquid-liquid phase separation (LLPS). We hypothesise that tensin enrichment and engagement with subsets of integrins is critical for the formation of FBs and that LLPS forms condensates that can act as a reservoir of signalling proteins. The use of structural biology combined with cell biology and advanced fluorescence microscopy will enable us to gain in-depth knowledge of how the different interactions are accompanied by structural changes of proteins in time and space and what consequences this has for the development of specific adhesion sites and downstream signalling pathways.

Insights from these studies may ultimately lead to the development of new strategies to prevent disease and promote tissue regeneration.