8.1 Principles of Mechanobiology

Mechanical forces shape our bodies at the cellular level. Mechanobiology explores how physical stimuli influence biological processes, from bone growth to blood vessel formation. This field combines biology, physics, and engineering to unlock the secrets of how cells respond to their physical environment.

Understanding mechanobiology is crucial for developing better biomaterials and tissue scaffolds. It helps engineers design more effective artificial tissues and organs, and aids in creating therapies for diseases like osteoporosis and atherosclerosis. The study of mechanotransduction reveals how cells convert physical forces into biochemical signals.

Fundamentals of Mechanobiology

Definition of mechanobiology

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• Mechanobiology studies how mechanical forces influence biological processes intersecting biology, physics, and engineering
• Enhances understanding of cellular responses to physical stimuli guiding development of biomaterials and tissue scaffolds
• Improves design of engineered tissues and organs aiding in developing therapies for mechanically-related diseases (osteoporosis, atherosclerosis)

Role of mechanical forces

• Types of mechanical forces shape cellular behavior: tension, compression, shear stress, hydrostatic pressure
• Influences cellular behaviors: proliferation, differentiation, migration, apoptosis
• Affects tissue development: bone remodeling responds to loading, blood vessel formation due to fluid shear stress, lung alveoli development influenced by breathing movements

Mechanisms and Structures in Mechanobiology

Concept of mechanotransduction

• Process converts mechanical stimuli into biochemical signals through various cellular mechanisms
• Stretch-activated ion channels open in response to membrane deformation allowing ion flux
• Focal adhesions transmit forces between extracellular matrix and cytoskeleton activating signaling cascades
• Cytoskeleton provides structural support and force transmission throughout the cell
• Nucleus responds to mechanical forces through changes in gene expression altering cellular function
• Signaling pathways involved: MAPK cascade regulates cell growth, calcium signaling triggers various cellular responses, Rho/ROCK pathway controls cytoskeletal reorganization

Importance of extracellular matrix

• Composition includes structural proteins (collagen, elastin), proteoglycans, and glycoproteins forming a complex network
• Provides physical support for cells and acts as a reservoir for growth factors and cytokines
• Transmits mechanical forces to cells through integrin-mediated adhesions triggering cellular responses
• ECM stiffness influences stem cell differentiation and cancer cell invasion by altering cellular mechanosensing
• Remodeling occurs in response to mechanical forces through matrix metalloproteinases (MMPs) activity and collagen fiber alignment
• Mechanosensing through cell-ECM interactions involves integrin clustering, activation, and formation of focal adhesion complexes