Lecture #16: Mechanics Mechanical Stretching

Boerboom et al. Effect of strain magnitude on the tissue properties of engineered cardiovascular constructs. Ann Biomed Eng (2008) vol. 36 (2) pp. 244-53 Mechanical Compression Mechanobiology is Fundamental

• Not restricted to muscle or bone cells

• Most cells can generate force – Comes from within the cell – Exerts contraction on surrounding ECM and cells

• These forces are essential to cellular function – Migration and mitosis – Proliferation and differentiation Mechanotransduction

• Tugging on ECM can deform proteins (e.g. fibronectin) to reveal previously hidden (cryptic) binding sites – Release of bound growth factors also possible

• Stretch-activated ion channels – Cardiac myocytes

• Integrins – Integrin binding and tension cause the formation of focal adhesions, which trigger further intracellular signaling Mechanisms of Mechanotransduction

Eyckmans et al. A hitchhiker's guide to mechanobiology. Developmental Cell (2011) vol. 21 (1) pp. 35-47 Cell-Cell: Adherens Junctions Nucleus Cell-Matrix: Focal Adhesion Focal Adhesion Complex

Cell Migration Lab, University of Reading Focal Adhesions

Red: fibers Green: Focal Adhesion Complexes

Lele TP, Thodeti CK, Ingber DE. J Cell Biochem. 2006 Apr 15;97(6):1175-83. Cell Attachment to ECM Integrins Must be Activated to Bind Signaling Happens In Both Directions

FA grows in response to external tugging (outside-in)

Internal contraction also results in FA growth and integrin activation (inside- out)

Figure 4.7, Van Blitterswijk Mechanotransduction Directs Differentiation Figure 1 0.26% 0.03% Bis- Bis-

Pelham and Wang, PNAS, 1997 Bitesize Bio, Biorad Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 The Protein Tethering Question Follow-Up Adipose Stromal Cells

Stain For- Osteogenic Differentiation

Stain For- Adipogenic Differentiation

Figure 1 Polyacrylamide Conjugation with ECM, with sulfo-SANPAH

Tse and Engler, Current Protocols in , 2010 No Significant Effect of SS Concentration on Differentiation

Figure 2