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Modelling The Combined Effects Of Collagen and Cyclic Strain On Cellular Orientation In Collagenous Tissues.

ABSTRACT: Adherent cells are generally able to reorient in response to cyclic strain. In three-dimensional tissues, however, extracellular collagen can affect this cellular response. In this study, a computational model able to predict the combined effects of mechanical stimuli and collagen on cellular (re)orientation was developed. In particular, a recently proposed computational model (which only accounts for mechanical stimuli) was extended by considering two hypotheses on how collagen influences cellular (re)orientation: collagen contributes to cell alignment by providing topographical cues (contact guidance); or collagen causes a spatial obstruction for cellular reorientation (steric hindrance). In addition, we developed an evolution law to predict cell-induced collagen realignment. The hypotheses were tested by simulating bi- or uniaxially constrained cell-populated collagen gels with different collagen densities, subjected to immediate or delayed uniaxial cyclic strain with varying strain amplitudes. The simulation outcomes are in agreement with previous experimental reports. Taken together, our computational approach is a promising tool to understand and predict the remodeling of collagenous tissues, such as native or tissue-engineered arteries and heart valves.

SUBMITTER: Ristori T

PROVIDER: S-EPMC5986791 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

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Modelling The Combined Effects Of Collagen and Cyclic Strain On Cellular Orientation In Collagenous Tissues.

Ristori T T Notermans T M W TMW Foolen J J Kurniawan N A NA Bouten C V C CVC Baaijens F P T FPT Loerakker S S

Scientific reports 20180604 1

Adherent cells are generally able to reorient in response to cyclic strain. In three-dimensional tissues, however, extracellular collagen can affect this cellular response. In this study, a computational model able to predict the combined effects of mechanical stimuli and collagen on cellular (re)orientation was developed. In particular, a recently proposed computational model (which only accounts for mechanical stimuli) was extended by considering two hypotheses on how collagen influences cellu ...[more]

PMID: 29867153

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Project description:As the fundamental structural protein in mammals, collagen transmits cyclic forces that are necessary for the mechanical function of tissues, such as bone and tendon. Although the tissue-level mechanical behavior of collagenous tissues is well understood, the response of collagen at the nanometer length scales to cyclical loading remains elusive. To address this major gap, we cyclically stretched individual reconstituted collagen fibrils, with average diameter of 145 ± 42 nm, to small and large strains in the partially hydrated conditions of 60% relative humidity. It is shown that cyclical loading results in large steady-state hysteresis that is reached immediately after the first loading cycle, followed thereafter by limited accumulation of inelastic strain and constant initial elastic modulus. Cyclic loading above 20% strain resulted in 70% increase in tensile strength, from 638 ± 98 MPa to 1091 ± 110 MPa, and 70% increase in toughness, while maintaining the ultimate tensile strain of collagen fibrils not subjected to cyclic loading. Throughout cyclic stretching, the fibrils maintained a steady-state hysteresis, yielding loss coefficients that are 5-10 times larger than those of known homogeneous materials in their modulus range, thus establishing damping of nanoscale collagen fibrils as a major component of damping in tissues. STATEMENT OF SIGNIFICANCE: It is shown that steady-state energy dissipation occurs in individual collagen fibrils that are the building blocks of hard and soft tissues. To date, it has been assumed that energy dissipation in tissues takes place mainly at the higher length scales of the tissue hierarchy due to interactions between collagen fibrils and fibers, and in limited extent inside collagen fibrils. It is shown that individual collagen fibrils need only a single loading cycle to assume a highly dissipative, steady-state, cyclic mechanical response. Mechanical cycling at large strains leads to 70% increase in mechanical strength and values exceeding those of engineering steels. The same cyclic loading conditions also lead to 70% increase in toughness and loss properties that are 5-10 times higher than those of engineering materials with comparable stiffness.

Dataset Information

Modelling The Combined Effects Of Collagen and Cyclic Strain On Cellular Orientation In Collagenous Tissues.

Publications

Modelling The Combined Effects Of Collagen and Cyclic Strain On Cellular Orientation In Collagenous Tissues.

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