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bioRxiv · 10.1101/2024.07.23.604866

Chiral mismatch in collagen-mimetic peptides modulates cell migration through integrin-mediated molecular recognition

Remson, A.·Dellemme, D.·luciano, M.·Surin, M.·Gabriele, S.
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Abstract

Chirality influences essential biological processes such as molecular recognition and self- organization, impacting cell proliferation and differentiation mediated by interactions with the extracellular matrix (ECM). Despite extensive research on cell migration, the role of chirality on matrix-cell interactions has been largely overlooked. To explore this aspect, we engineered culture surfaces coated with natural collagen I or collagen-mimetic peptides (CMPs) with opposite chirality, i.e. with either L- or D-amino acids in their sequences. Here we show that D-surfaces impede epithelial keratocyte spreading, making cells more rounded, less adhesive, and slower. Further investigation through integrin inhibition assays and molecular dynamics simulations revealed that a chiral mismatch destabilizes the triple helix of heterochiral CMPs at the L/D junction. This study underscores the profound impact of ECM chirality on cellular behavior, providing new insights into the relationship between matrix (supra)molecular chirality, integrin-mediated molecular recognition, and cell migration dynamics.

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Remson, A., Dellemme, D., luciano, M., Surin, M., Gabriele, S.. 2024-07-24. Chiral mismatch in collagen-mimetic peptides modulates cell migration through integrin-mediated molecular recognition. https://doi.org/10.1101/2024.07.23.604866

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