Mechanosensing using drag force for imaging soft biological membranes.

We investigate physical processes taking place during nanoscale mechanosensing of soft biological membranes in liquid environments. Examples include tapping mode imaging by atomic force microscope (AFM) and microscopy based on the Brownian motion of a nanoparticle in an optical-tweezers-controlled trap. The softness and fluidity of the cellular membrane make it difficult to accurately detect (i.e., image) the shape of the cell using traditional mechanosensing methods. The aim of the reported work is to theoretically evaluate whether the drag force acting on the nanoscale mechanical probe due to a combined effect of intra- and extracellular environments can be exploited to develop a new imaging mode suitable for soft cellular interfaces. We approach this problem by rigorous modeling of the fluid mechanics of a complex viscoelastic biosystem in which the probe sensing process is intimately coupled to the membrane biomechanics. The effects of the probe dimensions and elastic properties of the membrane as well as intra- and extracellular viscosities are investigated in detail to establish the structure and evolution of the fluid field as well as the dynamics of membrane deformation. The results of numerical simulations, supported by predictions of the scaling analysis of forces acting on the probe, suggest that viscous drag is the dominant force dictating the probe dynamics as it approaches a biological interface. The increase in the drag force is shown to be measurable, to scale linearly with an increase in the viscosity ratio of the fluids on either side of the membrane, and to be inversely proportional to the probe-to-membrane distance. This leads to the postulation of a new strategy for lipid membrane imaging by AFM or other mechanosensing methods using a variation in the maximum drag force as an indicator of the membrane position.