Abstract

Studies from the past two decades have demonstrated convincingly that cells are able to sense the mechanical properties of their surroundings. Cells make major decisions in response to this mechanosensation, including decisions regarding cell migration, proliferation, survival, and differentiation. The vast majority of these studies have focused on the cellular mechanoresponse to changing substrate stiffness (or elastic modulus) and have been conducted on purely elastic substrates. In contrast, most soft tissues in the human body exhibit viscoelastic behavior; that is, they generate responsive force proportional to both the magnitude and rate of strain. While several recent studies have demonstrated that viscous effects of an underlying substrate affect cellular mechanoresponse, there is not a straightforward experimental method to probe this, particularly for investigators with little background in biomaterial fabrication. In the current work, we demonstrate that polymers comprised of differing polydimethylsiloxane (PDMS) formulations can be generated that allow for control over both the strain-dependent storage modulus and the strain rate-dependent loss modulus. These substrates requires no background in biomaterial fabrication to fabricate, are shelf-stable, and exhibit repeatable mechanical properties. Here we demonstrate that these substrates are biocompatible and exhibit similar protein adsorption characteristics regardless of mechanical properties. Finally, we develop a set of empirical equations that predicts the storage and loss modulus for a given blend of PDMS formulations, allowing users to tailor substrate mechanical properties to their specific needs.

Highlights

  • The eld of mechanobiology has become a burgeoning eld of research

  • We demonstrate that polymers comprised of differing polydimethylsiloxane (PDMS) formulations can be generated that allow for control over both the strain-dependent storage modulus and the strain rate-dependent loss modulus

  • Discoveries that showed that the stiffness of substrates can drive cell migration, cell proliferation, and cell differentiation[1,2,3,4,5,6] were groundbreaking and created a paradigm where we could envision that the elastic modulus of in vivo tissue could be a key player in disease progression

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Summary

Introduction

The eld of mechanobiology has become a burgeoning eld of research. Discoveries that showed that the stiffness (elastic modulus) of substrates can drive cell migration, cell proliferation, and cell differentiation[1,2,3,4,5,6] were groundbreaking and created a paradigm where we could envision that the elastic modulus of in vivo tissue could be a key player in disease progression. There is a signi cant concern with drawing correlative conclusions from these studies: so tissue in the human body is viscoelastic,[17,18,19] and the majority of mechanobiology research has focused only on the elastic component. Viscoelastic materials can be quanti ed by the loss modulus, which represents the viscous component, and the storage modulus, which represents the elastic component. Most tissues in the human body exhibit viscoelastic behavior, with a loss modulus roughly 10 percent of the tissue's storage modulus.[20] Most so tissues in the body demonstrate viscoelastic properties that are subcategorized as “strain-stiffening materials”, where as the material stretches, it becomes effectively stiffer.[17,18,19,21] Loss moduli have been quanti ed for various tissues, including lung ($600 Pa),[22] brain ($1 kPa),[23] cornea ($12 kPa),[24] and liver

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