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

Public Health Relevance

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

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL098028-03
Application #
8400887
Study Section
Modeling and Analysis of Biological Systems Study Section (MABS)
Program Officer
Larkin, Jennie E
Project Start
2010-12-15
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
3
Fiscal Year
2013
Total Cost
$272,724
Indirect Cost
$106,124
Name
Boston University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
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Chow, Ming-Jay; Turcotte, Raphaƫl; Lin, Charles P et al. (2014) Arterial extracellular matrix: a mechanobiological study of the contributions and interactions of elastin and collagen. Biophys J 106:2684-92
Zeinali-Davarani, Shahrokh; Chow, Ming-Jay; Turcotte, Raphael et al. (2013) Characterization of biaxial mechanical behavior of porcine aorta under gradual elastin degradation. Ann Biomed Eng 41:1528-38
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Liu, Yuanming; Wang, Yunjie; Chow, Ming-Jay et al. (2013) Glucose suppresses biological ferroelectricity in aortic elastin. Phys Rev Lett 110:168101
Li, Jiangyu; Liu, Yuanming; Zhang, Yanhang et al. (2013) Molecular ferroelectrics: where electronics meet biology. Phys Chem Chem Phys 15:20786-96
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Liu, Yuanming; Zhang, Yanhang; Chow, Ming-Jay et al. (2012) Biological ferroelectricity uncovered in aortic walls by piezoresponse force microscopy. Phys Rev Lett 108:078103
Chow, Ming-Jay; Zou, Yu; He, Huamei et al. (2011) Obstruction-induced pulmonary vascular remodeling. J Biomech Eng 133:111009