The Effect of Thermal Fluctuation on the Receptor-Mediated Adhesion of a Cell Membrane to an Elastic Substrate

Mechanics of the bilayer membrane play an important role in many biological and bioengineering problems such as cell–substrate and cell–nanomaterial interactions. In this work, we study the effect of thermal fluctuation and the substrate elasticity on the cell membrane–substrate adhesion. We model the adhesion of a fluctuating membrane on an elastic substrate as a two-step reaction comprised of the out-of-plane membrane fluctuation and the receptor–ligand binding. The equilibrium closed bond ratio as a function of substrate rigidity was computed by developing a coupled Fourier space Brownian dynamics and Monte Carlo method. The simulation results show that there exists a crossover value of the substrate rigidity at which the closed bond ratio is maximal

The effect of viscous force on the prediction of muscle contractility in biohybrid cantilever-based experiments

The biohybrid cantilevers have been recently reported for high-throughput measurement of muscle contractility. In previous works, mechanical models were used to predict the contractile stress from the cantilever bending curvature. To derive those models, the cantilever bending process was considered as quasi-static and the viscous force was neglected. To ascertain the effect of the viscous force on the prediction of the muscle contractility in biohybrid cantilever-based experiments, we extend the modified Stoney’s equation to a dynamic model that takes into account both the viscous force and the inertia force. Parametric studies show that, because the viscous force hinders the movement of the cantilever, use of static models result in a system error between the calculated and true contractile stresses. When using static models, the diastolic stress will be over-estimated while the peak systolic stress will be under-estimated. The present work suggests that dynamic models can be used in biohybrid cantilever assays to calculate the muscle contractility with higher accuracy, or can be used to optimize the experimental parameters such that the error due to the use of static models is minimized

A minimal mechanics model for mechanosensing of substrate rigidity gradient in durotaxis

Durotaxis refers to the phenomenon in which cells can sense the spatial gradient of the substrate rigidity in the process of cell migration. A conceptual two-part theory consisting of the focal adhesion force generation and mechanotransduction has been proposed previously by Lo et al. to explain the mechanism underlying durotaxis. In the present work, we are concerned with the first part of the theory: how exactly is the larger focal adhesion force generated in the part of the cell adhering to the stiffer region of the substrate? Using a simple elasticity model and by assuming the cell adheres to the substrate continuously underneath the whole cell body, we show that the mechanics principle of static equilibrium alone is sufficient to account for the generation of the larger traction stress on the stiffer region of the substrate. We believe that our model presents a simple mechanistic understanding of mechanosensing of substrate stiffness gradient at the cellular scale, which can be incorporated in more sophisticated mechanobiochemical models to address complex problems in mechanobiology and bioengineering

Myofibrils in Cardiomyocytes Tend to Assemble Along the Maximal Principle Stress Directions

The mechanisms underlying the spatial organization of self-assembled myofibrils in cardiac tissues remain incompletely understood. By modeling cells as elastic solids under active cytoskeletal contraction, we found a good correlation between the predicted maximal principal stress directions and the in vitro myofibril orientations in individual cardiomyocytes. This implies that actomyosin fibers tend to assemble along the maximal tensile stress (MTS) directions. By considering the dynamics of focal adhesion and myofibril formation in the model, we showed that different patterns of myofibril organizations in mature versus immature cardiomyocytes can be explained as the consequence of the different levels of force-dependent remodeling of focal adhesions. Further, we applied the mechanics model to cell pairs and showed that the myofibril organizations can be regulated by a combination of multiple factors including cell shape, cell–substrate adhesions, and cell–cell adhesions. This mechanics model can guide the rational design in cardiac tissue engineering where recapitulating in vivo myofibril organizations is crucial to the contractile function of the heart

Effect of pressure profile of shock waves on lipid membrane deformation

Use of shock waves to temporarily increase the permeability of the cell membrane is a promising approach in drug delivery and gene therapy to allow the translocation of macromolecules and small polar molecules into the cytoplasm. Our understanding of how the characteristics of the pressure profile of shock waves, such as peak pressure and pulse duration, influences membrane properties is limited. Here we study the response of lipid bilayer membranes to shock pulses with different pressure profiles using atomistic molecular dynamics simulations. From our simulation results, we find that the transient deformation/disordering of the membrane depends on both the magnitude and the pulse duration of the pressure profile of the shock pulse. For a low pressure impulse, peak pressure has a dominant effect on membrane structural changes, while for the high pressure impulse, we find that there exists an optimal pulse duration at which membrane deformation/disordering is maximized

Reduced cardiac muscle power with low ATP simulating heart failure.

For patients with heart failure, myocardial ATP level can be reduced to one-half of that observed in healthy controls. This marked reduction (from ≈8 mM in healthy controls to as low as 3-4 mM in heart failure) has been suggested to contribute to impaired myocardial contraction and to the decreased pump function characteristic of heart failure. However, in vitro measures of maximum myofilament force generation, maximum shortening velocity, and the actomyosin ATPase activity show effective KM values for MgATP ranging from ≈10 μM to 150 μM, well below the intracellular ATP level in heart failure. Thus, it is not clear that the fall of myocardial ATP observed in heart failure is sufficient to impair the function of the contractile proteins. Therefore, we tested the effect of low MgATP levels on myocardial contraction using demembranated cardiac muscle preparations that were exposed to MgATP levels typical of the range found in non-failing and failing hearts. Consistent with previous studies, we found that a 50% reduction in MgATP level (from 8 mM to 4 mM) did not reduce maximum force generation or maximum velocity of shortening. However, we found that a 50% reduction in MgATP level caused a 20%-25% reduction in maximal power generation (measured during muscle shortening against a load) and a 20% slowing of cross-bridge cycling kinetics. These results suggest that the decreased cellular ATP level occurring in heart failure contributes to the impaired pump function of the failing heart. Since the ATP-myosin ATPase dissociation constant is estimated to be submillimolar, these findings also suggest that MgATP concentration affects cross-bridge dynamics through a mechanism that is more complex than through the direct dependence of MgATP concentration on myosin ATPase activity. Finally, these studies suggest that therapies targeted to increase adenine nucleotide pool levels in cardiomyocytes might be beneficial for treating heart failure