PT - JOURNAL ARTICLE AU - Matteo Chighizola AU - Tania Dini AU - Stefania Marcotti AU - Mirko D’Urso AU - Claudio Piazzoni AU - Francesca Borghi AU - Anita Previdi AU - Laura Ceriani AU - Claudia Folliero AU - Brian Stramer AU - Cristina Lenardi AU - Paolo Milani AU - Alessandro Podestà AU - Carsten Schulte TI - The glycocalyx affects the mechanotransductive perception of the topographical microenvironment AID - 10.1101/2021.03.02.433591 DP - 2022 Jan 01 TA - bioRxiv PG - 2021.03.02.433591 4099 - http://biorxiv.org/content/early/2022/03/07/2021.03.02.433591.short 4100 - http://biorxiv.org/content/early/2022/03/07/2021.03.02.433591.full AB - The cell/microenvironment interface is the starting point of integrin-mediated mechanotransduction, but many details of mechanotransductive signal integration remain elusive due to the complexity of the involved (extra)cellular structures, such as the glycocalyx.We used nano-bio-interfaces reproducing the complex nanotopographical features of the extracellular matrix to analyse the glycocalyx impact on PC12 cell mechanosensing at the nanoscale (e.g., by force spectroscopy with functionalised probes). Our data demonstrates that the glycocalyx configuration affects spatio-temporal nanotopography-sensitive mechanotransductive events at the cell/microenvironment interface. Opposing effects of glycocalyx removal were observed, when comparing flat and specific nanotopographical conditions. The excessive retrograde actin flow speed and force loading are strongly reduced on certain nanotopographies upon removal of the native glycocalyx, while on the flat substrate we observe the opposite trend.Our results highlight the importance of the glycocalyx configuration in a molecular clutch force loading-dependent cellular mechanism for mechanosensing of microenvironmental nanotopographical features.Competing Interest StatementThe authors have declared no competing interest.