A mechanism for sarcomere breathing: volume change and advective flow within the myofilament lattice

Abstract

TLD and SNS designed experiments. TLD, TCI, and SNS conducted the experiments. CDW extracted data from imaging. CDW, JAC, and SNS analyzed experimental data. JAC and TLD performed and analyzed the models. All contributed to the writing.

Fluid flow in the sarcomere

“…This model examines the interactions of flows and forces for an array of sliding filaments. This spatially explicit model also indicates that the analytical models applied in conjunction with the diffusion reaction advec-tion equation in [20] are good approximations of fluid flow in many sarcomeres. While this model does not account for the multiscale complexity of myriad interacting sarcomeres and exterior organelles within a muscle cell, it provides a first glimpse into the understudied problem of intrasarcomeric flows.…”

“…We have contrasted a finite element model of fluid flow in the sarcomere with two analytical models: the first is derived from kinematic constraints while the second follows from Darcy's law in which flow is proportional to the pressure gradient. Both analytical models were developed fully by Cass et al in an exploration of flow-mediated substrate transport in sarcomeres [20]. By creating a computational model which explicitly captures fluid flow around filaments we have explored the effect of varying the sarcomere length (i.e the filament overlap) and the drag forces on filaments as a function of their diameter.…”

“…While fluid flow generally augments substrate transport to the interior of the myofibril [20], the explicit nature of the flow field and its ramifications for substrate transport have not been investigated. Although the finite element model provides valuable information about how filaments structure flow within the sarcomere, at a larger scale the spatial arrangement of organelles on the outside of the myofibril (like the sarcoplasmic reticulum, mitochondria and t-tubules) may obstruct diffusion [28] and structure fluid flow.…”

“…Ultimately, each of the modeling methods we used searches for a possible solution to these equations subject to the boundary conditions posed by the geometry and motion of the sarcomere. Here we provide a brief explanation of the Darcy-based and kinematic-based fluid flow models which are fully developed by Cass et al [20].…”

“…Since the lattice of contractile machinery is not constrained to a constant volume [17,18,19], bulk fluid flow in addition to the flow driven by filament shearing must be coupled to diffusion. Using the diffusion, reaction, advection equation paired with analytical models of fluid flow in sarcomeres Cass et al demonstrated that, during cyclic contraction, bulk fluid movement augments substrate transport [20] over diffusion alone. We have expanded analyses of flow in the sarcomere by building a finite element model that captures the geometry of the sarcomere, and have contrasted the resulting flow field with these analytical models.…”