Tethering Cells via Enzymatic Oxidative Crosslinking Enables Mechanotransduction in Non-Cell-Adhesive Materials

Tom Kamperman*, Sieger Henke, João F Crispim, Niels G A Willemen, Pieter J Dijkstra, Wooje Lee, Herman L Offerhaus, Martin Neubauer, Alexandra M Smink, Paul de Vos, Bart J de Haan, Marcel Karperien, Su Ryon Shin, Jeroen Leijten

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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Cell-matrix interactions govern cell behavior and tissue function by facilitating transduction of biomechanical cues. Engineered tissues often incorporate these interactions by employing cell-adhesive materials. However, using constitutively active cell-adhesive materials impedes control over cell fate and elicits inflammatory responses upon implantation. Here, an alternative cell-material interaction strategy that provides mechanotransducive properties via discrete inducible on-cell crosslinking (DOCKING) of materials, including those that are inherently non-cell-adhesive, is introduced. Specifically, tyramine-functionalized materials are tethered to tyrosines that are naturally present in extracellular protein domains via enzyme-mediated oxidative crosslinking. Temporal control over the stiffness of on-cell tethered 3D microniches reveals that DOCKING uniquely enables lineage programming of stem cells by targeting adhesome-related mechanotransduction pathways acting independently of cell volume changes and spreading. In short, DOCKING represents a bioinspired and cytocompatible cell-tethering strategy that offers new routes to study and engineer cell-material interactions, thereby advancing applications ranging from drug delivery, to cell-based therapy, and cultured meat.

Originele taal-2English
Artikelnummer2102660
Aantal pagina's17
TijdschriftAdvanced materials
DOI's
StatusPublished - 3-sep-2021

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