Effect of Force Field Resolution on Membrane Mechanical Response and Mechanoporation Damage under Deformation Simulations

Abstract

Damage induced by transient disruption and mechanoporation in an intact cell membrane is a vital nanoscale biomechanical mechanism that critically affects cell viability. To complement experimental studies of mechanical membrane damage and disruption, molecular dynamics (MD) simulations have been performed at different force field resolutions, each of which follows different parameterization strategies and thus may influence the properties and dynamics of membrane systems. Therefore, the current study performed tensile deformation MD simulations of bilayer membranes using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) models to investigate how the damage biomechanics differs across atomistic and coarse-grained (CG) simulations. The mechanical response and mechanoporation damage were qualitatively similar but quantitatively different in the three models, including some progressive changes based on the coarse-graining level. The membranes yielded and reached ultimate strength at similar strains; however, the coarser systems exhibited lower average yield stresses and failure strains. The average failure strain in the UA model was approximately 7% lower than the AA, and the CG-M was 20% lower than UA and 27% lower than AA. The CG systems also nucleated a higher number of pores and larger pores, which resulted in higher damage during the deformation process. Overall, the study provides insight on the impact of force field-a critical factor in modeling biomolecular systems and their interactions-in inspecting membrane mechanosensitive responses and serves as a reference for justifying the appropriate force field for future studies of more complex membranes and more diverse biomolecular assemblies.

Keywords: All-atom; Bilayer membrane; Coarse-grained; Deformation; Force field; Mechanoporation; Molecular dynamics; United-atom.