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Matrix stiffness increases energy efficiency of endothelial cells
Curtis T Schunk1, Wenjun Wang1, Lindsey N Sabo1
1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA.
Summary
Stiffer extracellular matrix increases endothelial cell contractility and energy use. Increased matrix stiffness enhances cellular energy conversion into traction forces, crucial for blood vessel formation and tumor growth.
Area of Science:
- Cell Biology
- Biophysics
- Biochemistry
Background:
- Endothelial cells require energy for blood vessel formation (angiogenesis), involving cytoskeletal rearrangement, migration, and proliferation.
- Increased extracellular matrix stiffness promotes tumor angiogenesis and cell contractility, but the underlying mechanisms linking matrix properties, cell mechanics, and energy metabolism are unclear.
Purpose of the Study:
- To investigate the relationship between extracellular matrix stiffness, endothelial cell contractility, and cellular energy consumption.
- To elucidate how matrix stiffness influences the conversion of cellular energy into mechanical forces.
Main Methods:
- Utilized polyacrylamide substrates of varying stiffness.
- Employed a real-time adenosine triphosphate (ATP) biosensor to measure cellular energy usage.
- Applied traction force microscopy to quantify cell-generated forces.
Main Results:
- Endothelial cells showed increased traction forces and energy consumption with increasing substrate stiffness.
- Inhibition of Rho-associated coiled-coil kinase (ROCK) reduced cellular energy efficiency.
- Manganese treatment, promoting integrin affinity, led to increased energy efficiency.
Conclusions:
- A direct link exists between matrix stiffness, cell contractility, and cellular energetics.
- Endothelial cells on stiffer matrices are more efficient at converting intracellular energy into traction forces.
- Energy usage efficiency, not just production, is vital for regulating cell behaviors like angiogenesis.
