What is mechanobiology? How cell response to forces Forces the cell experience? ( Types of forces) Externally applied: • Fluid Shear Stress (fluid across cell it’s a frictional …) • Stretch (lung stretch) • Pressure (blood pressure) • ECM contraction, neighboring cells (stiffness of the ECM effect the cell ) Internally generated (endogenous): (cell it self can generate force) • Tension/compression generated by cytoskeleton • Motor proteins (If I add a drug that activates myosin then myosin will start to pull, that cell will exert more force on its surface.) What kind of tissues and cells experience force? Every cell in the body experience force Mechanical Forces these forces are critical to (play role in)? Development • Gastrulation • Heart development • Vasculogenesis Homeostasis Bone, muscle Vasculature, kidney, heart Skin, intestine Disease Cancer Atherosclerosis Deafness Three components of mechanotransduction? Mechanotransmissio, Mechanosensing and Mechanoresponse Proposed Mechanosensors? • Ion channels • Membrane tension • Cell-cell (cadherin) or cell-matrix (integrin) adhesions • Cytoskeleton • Glycocalyx • Primary Cilia The big advantage about mechanotransduction that it’s fast (mechanical vs chemical force propagation) mech is much faster. • The idea that you tug on the cell, within 5 micro seconds you got a force on the nucleus so its super fast • And if you have some diffusion event or receptor it might take 5 s or longer
Things that can affect the forces that the cell exert on its surface, ECM influence mech of cell The cell environment can dictate the shape of the cell Stiffness of the surface could affect the cell: So on the hard surface the cell really spreads out it’s focal adhesion on the edge of the cell you see a lot of filament across the cell, but on the soft surface the cell is rounded up . The concentration of substrate. If you change the ECM component you can change the cell. The space of the ligand The cell because it has cytoskeleton is what transmitting that force (Actin and intermediate filaments are the linkers(force transmitters)). Forces in : if you put force on the cell where does it go 1. Focal adhesion ( traction force promote stem cell differentiation ) 2. Cell-cell junction (mechanical tugging force regulates the size of the junction) 3. Nucleus (myosin controls nuclear force)you put force on a cell you trigger a response, a response being a different protein expression by altering gene expression at the DNA. Genetic and Epigenetic Changes Genetic: Changes in the DNA base pairs • Chemical : Local changes in DNA structure • Radiation : Non-specific breaks in DNA Can turn on and off gene , mutate P53 Will change the sequence of the chromosome Epigenetic: • Change in pattern of gene/protein expression without changing DNA base pair sequence.
You've reached the end of your free preview.
Want to read all 12 pages?
- Spring '14