Substrate Stiffness Affects Laminin-332 Matrix Deposition in Cultured Keretinocytes

Author(s):  
Abel L. Thangawng ◽  
Rodney S. Ruoff ◽  
Jonathan C. Jones ◽  
Matthew R. Glucksberg

It has been reported that the mechanical properties of a substrate influence cell motility, morphology, and adhesion [1–3]. This work is an attempt to move a step further beyond cells’ sensing the mechanical properties of their environment, by determining whether the secretion and assembly of laminin extracellular matrix is regulated by the mechanical environment in which the cell is placed. We hypothesize that this matrix then influences the behavior of the cell, particularly with regard to its motility.

2021 ◽  
pp. mbc.E21-03-0131
Author(s):  
Sarah Hyun Ji Kim ◽  
Daniel A. Hammer

To carry out their physiological responsibilities, CD4+ T lymphocytes interact with various tissues of different mechanical properties. Recent studies suggest that T cells migrate upstream on surfaces expressing ICAM-1 through interaction with LFA-1 integrins. LFA-1 likely interacts as a mechanosensor, and thus we hypothesized that substrate mechanics might affect the ability of LFA-1 to support upstream migration of T cells under flow. Here, we measured motility of CD4+ T lymphocytes on polyacrylamide gels with pre-determined stiffnesses containing ICAM-1, VCAM-1, or 1:1 mixture of VCAM-1/ICAM-1. Under static conditions, we found that CD4+ T cells exhibit an increase in motility on ICAM-1, but not on VCAM-1 or VCAM-1/ICAM-1 mixed, surfaces as a function of matrix stiffness. The mechanosensitivity of T cell motility on ICAM-1 is overcome when VLA-4 is ligated with soluble VCAM-1. Lastly, we observed that CD4+ T cells migrate upstream under flow on ICAM-1-functionalized hydrogels, independent of substrate stiffness. In summary, we show that CD4+ T cells under no flow respond to matrix stiffness through LFA-1, and that the crosstalk of VLA-4 and LFA-1 can compensate for deformable substrates. Interestingly, CD4+ T lymphocytes migrated upstream on ICAM-1 regardless of the substrate stiffness, suggesting that flow can compensate for substrate stiffness.


2019 ◽  
Vol 303 (6) ◽  
pp. 1703-1716 ◽  
Author(s):  
Obianamma E. Onochie ◽  
Anwuli J. Onyejose ◽  
Celeste B. Rich ◽  
Vickery Trinkaus‐Randall

Author(s):  
Frank X. Jiang ◽  
Uday Chippada ◽  
Lulu Li ◽  
Bernard Yurke ◽  
Rene S. Schloss ◽  
...  

Cells reside in a dynamic environment composed of extracellular matrix (ECM) and other cells, and take a variety of cues, of which mechanical stresses and strains are an important subset. ECM undergoes constant synthesis and degradation, and its mechanical stiffness can also be altered, with ageing, upon external assault or via pathological processes. Particularly in load barring tissues, the mechanical properties of the ECM can vary, by exposure to changing load conditions through, for example, collagen realignment. Tissue-implant interfaces also present medically important dynamic mechanical environment. Furthermore, recent studies revealed that the ranges of mechanical stiffness of ECM or substrates can alter specific cellular properties in distinct ways. From an engineering viewpoint, it is thus beneficial to be able to modify the physical properties of the biomaterials for the implants, providing optimal conditions for a specific desired outcome at different points during time progression. All of these reasons make it desirable to have a dynamic culture system with controlled property changes.


2018 ◽  
Author(s):  
Jingchen Feng ◽  
Herbert Levine ◽  
Xiaoming Mao ◽  
Leonard M. Sander

AbstractMechanical properties of the substrate plays a vital role in cell motility. Cells are shown to migrate up stiffness gradient (durotaxis) and along aligned fibers in the substrate (contact guidance). Here we present a simple mechanical model for cell migration, by placing a cell on lattice models for biopolymer gels and hydrogels. In our model cells attach to the substrate via focal adhesions (FAs). As the cells contract, forces are generated at the FAs, determining their maturation and detachment. At the same time, the cell also allowed to move and rotate to maintain force and torque balance. Our model, in which the cells only take the information of forces at the FAs, without a prior knowledge of the substrate stiffness or geometry, is able to reproduce both durotaxis and contact guidance.


2018 ◽  
Author(s):  
F. Saadat ◽  
M.J. Lagieski ◽  
V. Birman ◽  
S. Thomopoulos ◽  
G.M. Genin

AbstractThe extracellular matrix surrounding chondrocytes within cartilage and fibrocartilage has spatial gradients in mechanical properties. Although the function of these gradients is unknown, the potential exists for cells to tailor their mechanical microenvironment through these gradients. We hypothesized that these gradients enhance fluid transport around the cell during the slow loading cycles that occur over the course of a day, and that this enhancement changes the nature of the mechanical signals received at the surface of the cell. To test this hypothesis, we studied the effect of these gradients on the mechanical environment around a chondrocyte using a closed form, linearized model. Results demonstrated that functional grading of the character observed around chondrocytes in articular cartilage enhances fluid transport, and furthermore inverts compressive radial strains to provide tensile signals at the cell surface. The results point to several potentially important roles for functional grading of the pericellular matrix.


2021 ◽  
Author(s):  
Hao Li ◽  
Mengna Li ◽  
Pei Liu ◽  
Kai-Yang Wang ◽  
Haoyu Fang ◽  
...  

Due to the native skin limitations and the complexity of reconstructive microsurgery, advanced biomaterials are urgently required to promote wound healing for severe skin defects caused by accidents and disasters....


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shaohua Wu ◽  
Vikas Kumar ◽  
Peng Xiao ◽  
Mitchell Kuss ◽  
Jung Yul Lim ◽  
...  

AbstractHeart valve disease is a common manifestation of cardiovascular disease and is a significant cause of cardiovascular morbidity and mortality worldwide. The pulmonary valve (PV) is of primary concern because of its involvement in common congenital heart defects, and the PV is usually the site for prosthetic replacement following a Ross operation. Although effects of age on valve matrix components and mechanical properties for aortic and mitral valves have been studied, very little is known about the age-related alterations that occur in the PV. In this study, we isolated PV leaflets from porcine hearts in different age groups (~ 4–6 months, denoted as young versus ~ 2 years, denoted as adult) and studied the effects of age on PV leaflet thickness, extracellular matrix components, and mechanical properties. We also conducted proteomics and RNA sequencing to investigate the global changes of PV leaflets and passage zero PV interstitial cells in their protein and gene levels. We found that the size, thickness, elastic modulus, and ultimate stress in both the radial and circumferential directions and the collagen of PV leaflets increased from young to adult age, while the ultimate strain and amount of glycosaminoglycans decreased when age increased. Young and adult PV had both similar and distinct protein and gene expression patterns that are related to their inherent physiological properties. These findings are important for us to better understand the physiological microenvironments of PV leaflet and valve cells for correctively engineering age-specific heart valve tissues.


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