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Project

Smart hydrogels for optically mapping forces in 3D cancer models

Cellular traction forces mediate the physical interactions between cells and the extracellular matrix (ECM) and are crucial for cell migration and cancer invasion. It is known that cells physically remodel the ECM, and cellular forces are transmitted to distant cells through the matrix. However, due to the complex mechanics of natural ECMs, and the lack of suitable synthetic materials and analysis methods, little is known concerning the dynamics, spatial distribution, and transmission of cellular forces in 3D. During my Marie Curie project, I have shown for the first time that polyisocyanides (PIC) gels, as a synthetic fibrous material, are able to recreate the bi-directional cell-matrix interactions in a manner similar to natural ECMs. In this project, I will develop mechano-responsive hydrogels combining PIC polymers with DNA-based force modules, which can optically report and control cellular forces and fiber remodeling process. By using fibroblasts and cancer cells as model cells, we will study the role of cellular forces and force propagation in fibroblast activation and cancer cell interactions. The methods and materials developed will allow researchers to study how cellular forces affect the matrix, how far do they propagate within the matrix, and how are forces transmitted from the matrix to the distant cell, with subcellular resolution, in 3D. The insights acquired will allow us to shed light on the role of fibroblast-induced mechanical cues in cancer propagation.

Date:1 Oct 2022 →  Today
Keywords:Fibrous hydrogel, Cellular traction forces, 3D cancer model systems
Disciplines:Cellular interactions and extracellular matrix, Biomaterials, Molecular and cellular biomechanics