Defined dissipative properties to investigate the role of matrix viscosity on cellular response

The overall aim of this proposal is to produce materials with defined dissipative properties
to investigate the role of matrix viscosity on cellular response. Native tissues comprise
cells and a dynamic extracellular matrix, which provides mechanical and biochemical
cues responsible for guiding cell adhesion, proliferation and differentiation. The majority
of synthetic materials utilised in mechanotransduction research are produced solely with
defined elastic properties, providing a static environment for which cells can grow.
However, these materials fail to fully recapitulate the dissipative environment that cells
encounter in vivo (Cantini et al., 2019). Up to this point, little progress has been made in
understanding how cells respond to matrix viscosity and how this can be engineered to
influence cell fate. In this project, we propose to fabricate lipid-based and polymer-based
environments with defined range of viscous properties and controlled surface mobility.
These material platforms will be utilised to elucidate the underlying cellular mechanisms
behind cell response to matrix viscosity. Furthermore, functionalisation of these
materials with peptide ligands will be utilised to investigate interplay between cell
adhesion and matrix viscosity on cell behaviour. These platforms will improve our
understanding of how cells adhere and interact with viscous materials and how this
influences cell behaviour. Knowledge gained from these systems will then be
incorporated into the fabrication of bulk hydrogel systems, which will be engineered
with varying viscous properties, constant elastic properties and functionalised with
varying densities of peptide ligands. These hydrogel systems will be utilised to investigate
the interplay between matrix viscosity and elasticity on cell behaviour in two- and threedimensional environments. The outcomes of this project will improve our understanding
of cellular response to matrix viscosity, paving the way for engineering of advanced
materials with defined elastic and viscous properties for use in tissue engineering and
development of in vitro tissue models with physiologically relevant mechanical
properties.
References
Cantini, M. et al. (2019) 'The Plot Thickens: The Emerging Role of Matrix Viscosity in Cell
Mechanotransduction', Advanced Healthcare Materials. doi: 10.1002/adhm.201901259.