With the current development of non-invasive diagnostics to more accurately measure the level of cardiovascular diseases (CVDs) clinically, a significant ?platform science? component is better mechanistic understanding of underlying physics, such as structure-function mechanics of the arterial wall. Much of this fundamental understanding comes from the development and study of models for biomechanics, which will provide guidance for developing diagnostics, and implementation of these diagnostics to the clinical setting in turn provides data for refining the physics models. In this project, we seek to develop a multiscale predictive mechanobiology model of extracellular matrix (ECM) mechanics from a fundamental mechanics perspective coupled with critical biophysical input, and to provide a clinical relevant relationship between biomechanical integrity, biochemical composition stability, and microstructure of the ECM. Such model will enable researchers and clinicians to probe basic mechanisms, and to assist in rational design of new therapies for CVD.
Specific Aim 1 : Create a multiscale predictive mechanobiology model of ECM mechanics. Molecular ? fiber level: a statistical mechanics based approach is adopted to determine the strain energy change accompanying deformation of a single fiber. A freely joined chain (FJC) model will be adopted to describe the possible configurations, thus entropy, of a fiber during stretching. Inter-molecular cross-linking density is a material parameter that determines the extensibility of a single fiber. Fiber ? tissue level: advance the fiber-level model into a tissue-level model by incorporating fiber distribution function and adding fiber density as the next set of material parameter. A multiscale mechanobiological model that incorporates inter-molecular cross-linking, fiber distribution and fiber density will be achieved for the description of tissue-level function.
Specific Aim 2 : Validation of the model using an integrated experimental ? modeling approach. Tissue-level ECM mechanics: the tissue-level behavior of ECM network will be fully characterized using biaxial-tensile test. Elastin and collagen network will be isolated from aortic tissue and tested individually. Fiber distribution function: the fiber orientation information of elastin and collagen will be obtained using confocal microscopy and directly incorporated into the model. Fiber density and cross-linking: the content and crosslinking density of elastin and collagen will be measured biochemically through biological assay. Corresponding material parameters in the model will be determined from fits to the biaxial-tensile testing data. 1
In this project, we seek to develop a multiscale predictive mechanobiology model for the study of extracellular matrix mechanics from a fundamental mechanics perspective coupled with critical biophysical input. The proposed work will be accomplished through two specific aims that couple modeling and experimental work for a complete model development and validation. Results from this research will provide clinical relevant relationship between biomechanical integrity, biochemical composition stability, and microstructure of the ECM. 1
|Yu, Xunjie; Wang, Yunjie; Zhang, Yanhang (2018) Transmural variation in elastin fiber orientation distribution in the arterial wall. J Mech Behav Biomed Mater 77:745-753|
|Wang, Yunjie; Hahn, Jacob; Zhang, Yanhang (2018) Mechanical Properties of Arterial Elastin With Water Loss. J Biomech Eng 140:|
|Zhang, Yanhang; Li, Jiangyu; Boutis, Gregory S (2017) The Coupled Bio-Chemo-Electro-Mechanical Behavior of Glucose Exposed Arterial Elastin. J Phys D Appl Phys 50:|
|Mattson, Jeffrey M; Turcotte, Raphaël; Zhang, Yanhang (2017) Glycosaminoglycans contribute to extracellular matrix fiber recruitment and arterial wall mechanics. Biomech Model Mechanobiol 16:213-225|
|Mattson, Jeffrey M; Zhang, Yanhang (2017) Structural and Functional Differences Between Porcine Aorta and Vena Cava. J Biomech Eng 139:|
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|Wang, Yunjie; Zeinali-Davarani, Shahrokh; Zhang, Yanhang (2016) Arterial mechanics considering the structural and mechanical contributions of ECM constituents. J Biomech 49:2358-65|
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|Silverstein, Moshe C; Bilici, Kübra; Morgan, Steven W et al. (2015) 13C, 2h NMR studies of structural and dynamical modifications of glucose-exposed porcine aortic elastin. Biophys J 108:1758-1772|
|Fry, Jessica L; Shiraishi, Yasunaga; Turcotte, Raphaël et al. (2015) Vascular Smooth Muscle Sirtuin-1 Protects Against Aortic Dissection During Angiotensin II-Induced Hypertension. J Am Heart Assoc 4:e002384|
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