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Quantification of local matrix deformations and mechanical properties during capillary morphogenesis in 3D
Ekaterina Kniazeva1, John W Weidling, Rahul Singh
1Biomedical Engineering Department, Natural Sciences II, Room 3201, University of California, Irvine, Irvine, CA 92697-2715, USA.
Integrative Biology : Quantitative Biosciences From Nano to Macro
|January 28, 2012
Summary
Endothelial cells (ECs) drive capillary sprouting by deforming the extracellular matrix (ECM). This study quantifies cell-ECM interactions, revealing how cell-generated forces and local ECM stiffening influence capillary morphogenesis.
Area of Science:
- Cell biology
- Biophysics
- Biomaterials science
Background:
- Cell-extracellular matrix (ECM) mechanical interactions are crucial for tissue development.
- Previous studies lacked microscale characterization of these interactions in 3D matrices.
- Understanding these dynamics is key to comprehending branching morphogenesis.
Purpose of the Study:
- To quantify endothelial cell (EC)-mediated deformations of ECM elements.
- To measure local ECM mechanical properties during capillary morphogenesis.
- To correlate microscale cell-ECM dynamics with macroscale tissue formation.
Main Methods:
- Spatio-temporal image correlation spectroscopy (STICS) to track ECM fiber deformation by ECs.
- Laser optical tweezers-based active microrheology (AMR) to measure local ECM stiffness.
- 3D cell culture models to mimic in vivo conditions.
Main Results:
- Microscale ECM deformation rates by ECs positively correlated with macroscale capillary sprouting.
- Active RhoA signaling in ECs enhanced both ECM deformation and capillary sprouting.
- A local stiffening of the ECM near sprouting EC tips was observed.
- A direct correlation was found between microscale ECM dynamics and macroscale capillary morphogenesis.
Conclusions:
- Quantified the dynamic physical properties of the cell-ECM interface in space and time.
- Established a link between microscale ECM deformation/stiffening and macroscale capillary morphogenesis.
- Provided novel insights into the mechanical regulation of angiogenesis.
