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Controlled Deposition of 3D Matrices to Direct Single Cell Functions.

ABSTRACT: Advances in engineered hydrogels reveal how cells sense and respond to 3D biophysical cues. However, most studies rely on interfacing a population of cells in a tissue-scale bulk hydrogel, an approach that overlooks the heterogeneity of local matrix deposition around individual cells. A droplet microfluidic technique to deposit a defined amount of 3D hydrogel matrices around single cells independently of material composition, elasticity, and stress relaxation times is developed. Mesenchymal stem cells (MSCs) undergo isotropic volume expansion more rapidly in thinner gels that present an Arg-Gly-Asp integrin ligand. Mathematical modeling and experiments show that MSCs experience higher membrane tension as they expand in thinner gels. Furthermore, thinner gels facilitate osteogenic differentiation of MSCs. By modulating ion channels, it is shown that isotropic volume expansion of single cells predicts intracellular tension and stem cell fate. The results suggest the utility of precise microscale gel deposition to control single cell functions.

SUBMITTER: Wong SW

PROVIDER: S-EPMC7578851 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Controlled Deposition of 3D Matrices to Direct Single Cell Functions.

Wong Sing Wan SW Lenzini Stephen S Bargi Raymond R Feng Zhe Z Macaraniag Celine C Lee James C JC Peng Zhangli Z Shin Jae-Won JW

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20200903 20

Advances in engineered hydrogels reveal how cells sense and respond to 3D biophysical cues. However, most studies rely on interfacing a population of cells in a tissue-scale bulk hydrogel, an approach that overlooks the heterogeneity of local matrix deposition around individual cells. A droplet microfluidic technique to deposit a defined amount of 3D hydrogel matrices around single cells independently of material composition, elasticity, and stress relaxation times is developed. Mesenchymal stem ...[more]

PMID: 33101850

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Project description:Cell motility under physiological and pathological conditions including malignant progression of cancer and subsequent metastasis are founded on environmental confinements. During the last two decades, three-dimensional cell migration has been studied mostly by utilizing biomimetic extracellular matrix models. In the majority of these studies, the in vitro collagen scaffolds are usually assumed to be homogenous, as they consist commonly of one specific type of collagen, such as collagen type I, isolated from one species. These collagen matrices should resemble in vivo extracellular matrix scaffolds physiologically, however, mechanical phenotype and functional reliability have been addressed poorly due to certain limitations based on the assumption of homogeneity. How local variations of extracellular matrix structure impact matrix mechanics and cell migration is largely unknown. Here, we hypothesize that local inhomogeneities alter cell movement due to alterations in matrix mechanics, as they frequently occur in in vivo tissue scaffolds and were even changed in diseased tissues. To analyze the effect of structural inhomogeneities on cell migration, we used a mixture of rat tail and bovine dermal collagen type I as well as pure rat and pure bovine collagens at four different concentrations to assess three-dimensional scaffold inhomogeneities. Collagen type I from rat self-assembled to elongated fibrils, whereas bovine collagen tended to build node-shaped inhomogeneous scaffolds. We have shown that the elastic modulus determined with atomic force microscopy in combination with pore size analysis using confocal laser scanning microscopy revealed distinct inhomogeneities within collagen matrices. We hypothesized that elastic modulus and pore size govern cancer cell invasion in three-dimensional collagen matrices. In fact, invasiveness of three breast cancer cell types is altered due to matrix-type and concentration indicating that these two factors are crucial for cellular invasiveness. Our findings revealed that local matrix scaffold inhomogeneity is another crucial parameter to explain differences in cell migration, which not solely depended on pore size and stiffness of the collagen matrices. With these three distinct biophysical parameters, characterizing structure and mechanics of the studied collagen matrices, we were able to explain differences in the invasion behavior of the studied cancer cell lines in dependence of the used collagen model.

Dataset Information

Controlled Deposition of 3D Matrices to Direct Single Cell Functions.

Publications

Controlled Deposition of 3D Matrices to Direct Single Cell Functions.

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