Mechanistic Control of Cell Adhesion at Ligand-free Soft Membrane Interfaces

Abstract Cell adhesion at soft interfaces is governed by a complex interplay between interaction forces and interfacial dynamics whose relative contributions remain difficult to disentangle. Here, we investigate the adhesion of yeast cells (Saccharomyces cerevisiae) on supported lipid bilayers with controlled composition, including systems containing the glycolipid ohmline (OHM), which serve as well-defined model membrane interfaces. By combining QCM-D measurements with interfacial characterization, including dilatational rheology, we show that adhesion proceeds through two kinetically distinct regimes governed by different physical mechanisms. The initial stage is dominated by electrostatic interactions, as evidenced by the correlation of the characteristic time with the membrane zeta potential. In contrast, the second stage is governed by membrane viscoelasticity, with the adsorption kinetics scaling with the dilatational modulus, indicating that the postcontact dynamics is limited by interfacial relaxation. Variations in membrane composition modulate hydration, molecular packing, and energy dissipation, thereby influencing adhesion behavior. OHM-containing systems exhibit enhanced sensitivity to ionic conditions and a more dissipative viscoelastic response, leading to stronger cell–membrane coupling. In mixed membranes, the interplay between electrostatics and viscoelasticity enables a decoupling of adhesion regimes, where initial attachment and subsequent interfacial reorganization are governed by distinct mechanisms. These results establish a quantitative framework linking adhesion kinetics to intrinsic membrane properties, identifying zeta potential and viscoelasticity as complementary parameters governing distinct adhesion regimes. Together, they provide insight into how electrostatics, hydration, and interfacial mechanics regulate cell adhesion at soft interfaces and demonstrate that adhesion can be tuned through membrane composition without specific adhesion ligands.