IBEC’s Nanobioengineering group have made important inroads in mechanobiology by creating an in vitro model of the extracellular matrix that shows how this environment works with protein complex actomyosin – the essential substance that allows muscle to contract – to direct the movement of cells.
The group’s paper, which appears in Advanced Functional Materials this week, sheds light on cell migration, which is essential for many biological processes such as embryonic development and wound healing when things are going right, and cancer progression when things go wrong.
These images show collagen (grey) and fibronectin (red) on the native-like matrices engineered by IBEC’s Nanobioengineering group. The top row shows disordered (isotropic) matrices and the bottom row aligned (anisotropic) ones, with white arrows indicating the orientation. Pink shows the merged images, and the last panels show a cross-correlation analysis.
So far, we know that the physical properties of the extracellular matrix (ECM), including its topology, mechanical properties, and molecular composition, are physical cues that synergize with molecular factors such as actomyosin contractility – the mechanism that generates mechanical stress in animal cells so that muscles can contract, tissue can develop and cells can divide – to regulate cell migration.
It’s a challenge to study these synergies, though, because while the topology of the matrix is difficult to control in vivo, micro-engineered models in vitro lack the biochemical and physical complexity of the native environment. The researchers needed to come up with a solution that allowed the study of a faithful representation of the ECM’s physical properties interacting with the real molecular factors that are found in the body.
Working in collaboration with colleagues at the International Iberian Nanotechnology Laboratory (INL) in Braga, Portugal, IBEC director Josep Samitier’s group seeded cells onto polarized 3D matrices that mimicked the structural and biochemical features of the in vivo extracellular matrix, including its topology, which was either anisotropic (aligned) or isotropic (disordered). They found that the direction of cell movement, but not distance, is enhanced when the engineered matrices are topologically anisotropic, but when they are not – when they are isotropic – cell directionality was independent of actomyosin contractility.
They could therefore conclude that, for directed cell motion, a synergy of actomyosin contractility with anisotropy is required. They also noted that anisotropy counteracts a lack of actomyosin-driven forces to enhance the ability of cells to move or invade, and to stabilize their directionality.
Such important insights into the biophysical mechanisms of directed cell migration in native-like environments may have important implications for the understanding of critical processes where directional cell motility is involved, such as in cancer or embryonic development.
Source article: David Caballero, Lucas Palacios, Paulo P. Freitas, Josep Samitier (2017). “An Interplay Between Matrix Anisotropy and Actomyosin Contractility Regulates 3D Directed Cell Migration“. Advanced Functional Materials, epub ahead of print.
The authors acknowledge the Beatriu de Pinós postdoctoral fellowship (COFUND MSCA) of David Caballero to carry out this work at IBEC, and MINECO’s “Explora Ciencia” programme.