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Cardiac mechanics and adaptive remodeling in hypertension

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Scanning Electron Microscopy of Left Rat VentricleThe overarching goal of this project is to elucidate the mechanical interaction between cells and collagen fiber network in normal and diseased hearts to understand fundamentally the role of this interaction in affecting ventricular mechanics during pathological remodeling. Myocyte hypertrophy (increased size of cells) and fibrosis (increased synthesis and deposition of collagen fibers) coexist in myocardial remodeling caused by hypertension, which affects one out of three adults in the U.S. Although it is generally known that myocytes and the collagen fiber network both affects ventricular mechanics and can interact mechanically within the heart tissue, it is not known how they interact and how the interaction affects the mechanics and adaptation of the tissue. In the past three years, my group collected experimental data and implemented a novel mechanical model, for normal and hypertensive rat hearts, suggesting that the mechanical coupling between the cells and the collagen fibers network, arising from their physical contact, can play a crucial role in myocardial mechanics.

Collaborators: Prof. L.C. Lee (Mechanical Eng. Dept., MSU), Prof. S. Watts and Prof. G. Fink (both, Pharmacology & Toxicology Dept., MSU), Prof. M. Dantus (Chemistry Dept., MSU).

Impact.This study has broad impacts on both fundamental and applied areas of biology and human health. At the fundamental level, the study has the potential to transform our understanding of tissue mechanics, because cells and collagen fibers are key constituents of biological tissues, while both collagen fiber synthesis/degradation and cellular hypertrophy are fundamental biological processes. In terms of applications, this study has a significant impact on human health, as its findings are relevant to new emerging heart failure treatments, such as regenerative medicine, where cell-matrix interaction a key factor responsible for the success of engineered tissues.

Future Directions. The long-term goal is to develop a methodology to quantify and incorporate the mechanical interaction between collagen and cells into existing constrained mixture models used to describe the growth and remodeling of the heart.

 

References

         Grobbel M.R., Lee L.C., Watts S.W., Fink G.D., Roccabianca S. (2020) Left ventricular geometry, tissue composition, and residual stress in High Fat Diet Dahl-Salt sensitive rats. Experimental Mechanics, https://doi.org/10.1007/s11340-020-00664-8.

         Grobbel M.R., Shavik S.M., Darios E., Watts S.W., Lee L.C., Roccabianca S. (2018) Contribution of left ventricular residual stress by myocytes and collagen: existence of inter-constituent mechanical interaction. Biomechanics and Modeling in Mechanobiology, 17(4), 985–999.

 

Presentations, proceedings, and papers

         Roccabianca S., Grobbel M., Shavik S.M., Watts S.W., Lee L.C. the role of inter-constituent mechanical interaction in left ventricular mechanics. 13th World Congress on Computational Mechanics (WCCMXIII). July 22-27, 2018. New York City, NY. (Keynote talk)

            Roccabianca S.Mechanical coupling in soft biological tissues: a new force driving growth and remodeling. AEM Colloquium Series. October 11, 2019. University of Minnesota, Aerospace Engineering and Mechanics Department. Minneapolis, MN. (Invited seminar)

            Roccabianca S., Grobbel M.R., Shavik S.M., Watts S.W., Lee L.C. Inter-constituent interaction in soft biological tissues: What do cells really feel? Michigan State University, Science at the Edge seminar series. March 30, 2018. East Lansing, MI. (Invited seminar)

         Grobbel M., Fink G., Watts S., Lee L.C., Roccabianca S. Effects of hypertension-induced remodeling on the mechanics of the left ventricle. 16th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering (CMBBE2019). August 14-16, 2019. New York City, NY. (Podium presentation)

         Grobbel M., Shavik S.M., Darios E., Watts S.W., Lee L.C., Roccabianca S. Examination of left ventricular inter-constituent interaction and its effect on residual stress. 8th World Congress of Biomechanics. July 8-12, 2018. Dublin, Ireland. (Podium presentation)

         Grobbel M., Shavik S.M., Darios E., Watts S.W., Lee L.C., Roccabianca S. Contribution of collagen fibers and myocytes to residua stress in the left ventricular wall. Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C). June 21–24, 2017. Tucson, AZ. (Poster presentation)

         Shavik S.M., Grobbel M., Lee L.C., Roccabianca S. Myocytes-collagen interaction in the heart: and experimentally-guided modeling study. Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C). June 21–24, 2017. Tucson, AZ. (Poster presentation)

         Grobbel M., Shavik S.M., Darios E., Watts S.W., Lee L.C., Roccabianca S. Integrated experimental-modeling approach to elucidate myocyte-collagen interaction in the ventricular wall. 5th International Conference on Computational and Mathematical Biomedical Engineering. April 10–12 2017. Pittsburgh, PA. (Podium presentation)

         Grobbel M., Lee L.C., Roccabianca S., Shavik SM. Contribution of collagen fibers and cardiac muscle cells to residual stress in the left ventricle wall. Mechbio Symposium, San Diego, CA, August 4-5, 2016 (Poster Presentation)