Here, we recreate for the first time the bi-directional cell-matrix physical interactions observed in biological hydrogels using synthetic hydrogels formed from polyisocyanide polymers (PIC). Our results show that PIC gels respond to cellular tractions in a manner similar to natural ECMs. Cells are able to physically induce fibre alignment and densification in the pericellular region, creating tunnels to migrate through the PIC matrix. Cellular traction forces can generate extensive fibre displacements and present a long-range stress propagation through the fibrous network. These physical interactions eventually increase the bulk storage moduli of cell-containing gels, as shown by a combination of three–dimensional traction force microscopy (3D TFM) and live-cell rheological tests. Together with the analysis of matrix remodelling, we elucidated that matrix stiffening arises from the cell-induced strain-stiffening and the rearrangement of fiber network by plastic remodelling. Both these phenomena are caused by cellular traction forces, but occur at different time scales. To further demonstrate the potential of this material to decipher the complex cell-matrix physical interactions, we investigated how changes in the mechanical or biochemical properties of PIC matrices were related to cell morphology, matrix remodeling and deformation, and force propagation. Notably, PIC gels showed cell-induced mechanical dynamics comparable with those observed in collagen and Matrigel matrices, while possessing a custom design manner. Our work showcases the flexible applications of synthetic fibrous networks in providing insights into cell-matrix interactions and paving the way for the rational design of improved biomaterials for the understanding of matrix biology.
In terms of the outreach activities, as a committee member, we organized a ‘SUMMER SCHOOL: FEEL THE FORCE’ together with the group of Prof. Dr. Hans van Oosterwyck (KU Leuven) on 15-17th Sept. 2021 (
https://www.kuleuven.be/english/summer-schools/feeltheforce/home(si apre in una nuova finestra)). I presented my results acquired during this fellowship in a talk (Title: Synthetic fibrous hydrogels as a platform to decipher cell-matrix physical interactions). The summer school attracted more than 30 ‘force lovers’ from many different labs within Europe (Belgium, the Netherlands, France, and Germany).
Apart from this, the results were also disseminated in conferences, namely MechanoChemBio2021, CHAINS, EACR-AACR-ASPIC Conference on Tumor Microenvironment, and in intra-department symposiums that involved both poster and oral presentation. Unfortunately, the COVID-imposed restrictions did not allow participation in other events.
We are currently finishing two article publications related to this project, one is submitted, and a second one is under preparation.
