Abstract

Recent evidence has led to the hypothesis that dissipation of energy through the viscoelastic extracellular matrix (ECM) can play a cardinal role in directing cell‐fate decisions, but whether and how it correlates with specific cell response is at present unclear. Here, viscoelastic and plastic 2D chitosan‐based substrates endowed with different dissipative energies are developed and cell behavior studied in terms of adhesion and spreading. While keeping constant stress relaxation and systematically decoupling overall stiffness from linear elongation, an energy dissipation term (J mol⁻¹) is introduced, that is the molar energy required to deviate from linear stress–strain regime and enter into plastic region. Strikingly, an inverse relationship is unveiled between substrate dissipation energy and cell response, with high adhesion/high spreading and low adhesion/no spreading detected for substrates at low and high dissipation energy, respectively. It is concluded that cells decide how to react depending on the effective energy they can earmark for their functions.