Fatty acids in cellular membranes nonspecifically impact cardiovascular function though Piezo1 activity

Project: Research project

Project Details

Description

Dietary fatty acids function in many processes that impact cardiovascular health. Omega-3 polyunsaturated fatty acid (PUFA) treatment has shown promising results in cardiac patients. However, the mechanism and broad consequences of this treatment is poorly understood. Aside from being an efficient energy source, PUFAs insert into cellular membranes and alter the membrane composition. These membrane composition changes have been shown to impact the function of a diverse range of proteins. However, the precise effects of membrane composition changes and many of the protein targets of PUFAs remain unknown. One way that membrane composition changes may affect membrane protein function is by changing the global mechanical properties of cell membranes. It is hypothesized that PUFAs act on membrane proteins by altering global mechanical properties. However, the individual roles of PUFA chain length, degree of unsaturation, and location of the unsaturated bond(s) on membrane mechanical properties and protein activity are yet to be determined. We propose that these structural features of PUFAs alter bilayer mechanical properties such as bending rigidity, fluidity, and area expansion modulus. Our approach to investigate this relationship is to incorporate PUFAs of different chain lengths and degrees of unsaturation into phospholipid vesicles. Then, using mechanical characterization techniques such as micropipette aspiration and quantitative fluorescent assays we will uncover the effects of dietary PUFAs on stiffness, bending rigidity, and fluidity respectively. Finally, we will put our results into a physiological context and explore how PUFAs affect the mechanical properties of red blood cells (RBCs) when added directly to these cells. Finally, we will investigate the effect of PUFAs on a model mechanosensitive channel protein, Piezo1, an RBC protein involved in microvascular tone. By demonstrating this system in model and cellular membranes, we will determine the extent to which PUFA insertion changes membrane properties and Piezo1 dynamics. Our findings will provide a mechanistic understanding of how PUFAs alter membrane properties and the extent to which these membrane properties influence membrane protein activity. As we gain a deeper understanding of how PUFAs aid cardiovascular health, our results will enable the development of therapeutic amphiphiles similar to PUFAs.
StatusActive
Effective start/end date1/1/2012/31/21

Funding

  • American Heart Association (20PRE35180215)

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