272544 The Impact of External Shear Forces On the Transport of Cell Membrane Species in Heterogeneous Lipid Bilayers
The impact of external shear forces on the transport of cell membrane species in heterogeneous lipid bilayers
Many biological processes in the cell are controlled by interactions between biomolecules residing in the cell membrane. Interactions between these species can be controlled and facilitated by the local membrane composition and the affinity of the species for a particular membrane type. The cell membrane has distinct lipid micro-domains of co-existing phases, called lipid raft and liquid-disordered phases, and this feature has been suggested to play a key role in regulating several cellular activities, as some proteins have been shown to exhibit different activity levels depending on specific lipid interactions.
However, studying dynamic changes in biomolecule partitioning between different lipid phases and identifying stimuli that may change affinity for a particular phase has been a significant challenge for researchers. Either the experimental approaches used in vivo result in too many artifactual consequences (i.e. detergent contamination, multivalent labeling enrichment), or they are limited by in vitro methods that can only assess equilibrium conditions.
Our group recently developed a new in vitro approach to study kinetics of partitioning using patterned heterogeneous supported lipid bilayers (SLB) inside a microfluidic device. The patterned heterogeneous SLBs system is a native-like membrane environment that removes the drawbacks of the previous approaches since it allows membrane species to retain their native structure, fluidity, and functionality. Using this approach, we are able to study how external shear forces impact biomolecule partitioning between heterogeneous lipid phases and facilitate interactions among membrane-bound species.
In this study, we developed an analytical model that we validated with experiments using fluorescent tracers to report on the velocity of biomolecules within the supported bilayers. This model helps us to determine the velocity profile in the interfacial regions between two phases. With this information, we are able to characterize the transport behavior of membrane-bound species subjected to external shear stress to determine the influence of shear forces on the partitioning process in heterogeneous membranes. We suggest that this platform can be used for studying heterogeneous cell membrane environments that is subjected to shear, such as in epithelial tissue. Such studies might contribute to our understanding of biological function in the vasculature and disease processes that occur there, such as atherosclerosis.