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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 forceon its surface.)What kind of tissues and cells experience force? Every cell in the body experience forceMechanical Forces these forces are critical to (play role in)?Development•Gastrulation•Heart development•VasculogenesisHomeostasisBone, muscleVasculature, kidney, heart Skin, intestineDiseaseCancerAtherosclerosisDeafnessThree components of mechanotransduction?Mechanotransmissio, Mechanosensing and MechanoresponseProposed Mechanosensors?•Ion channels•Membrane tension•Cell-cell (cadherin) or cell-matrix (integrin) adhesions•Cytoskeleton•Glycocalyx•Primary CiliaThe big advantage about mechanotransductionthat it’s fast (mechanical vs chemical forcepropagation) mech is much faster.•The idea that you tug on the cell, within 5 micro seconds you got a force on thenucleus 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 cellThe cell environment can dictate the shape of the cell Stiffness of the surface could affect the cell: So on the hard surface the cell reallyspreads out it’s focal adhesion on the edge of the cell you see a lot of filament acrossthe cell, but on the soft surface the cell is rounded up .The concentration of substrate. If you change the ECM component you can changethe cell.The space of the ligand The cell because it has cytoskeleton is what transmitting that force (Actin and intermediatefilaments are the linkers(force transmitters)).Forces in : if you put force on the cell where does it go1.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, aresponse being a different protein expression by altering gene expression at the DNA.Genetic and Epigenetic ChangesGenetic: Changes in the DNA base pairs •Chemical : Local changes in DNA structure•Radiation : Non-specific breaks in DNACan 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 pairsequence.