till dec 4 bio slides

Smooth Muscle Overview

• Characteristics of Smooth Muscle

  • Loose Organization: Smooth muscle cells are loosely organized allowing them to function even when stretched significantly.

  • Regeneration Ability: Unique among muscle tissues in their capacity to regenerate fully.

  • Functional in Stretch: Adaptability makes them ideal for tubular organs that require stretch, such as blood vessels.

Learning Objectives

• Students should be able to:

  • Explain force generation on actin filaments via myosin motor protein.

  • Describe optical methods for measuring forces on single molecules.

  • Summarize actin/myosin interactions in striated muscle.

  • Apply principles from striated muscle contraction to smooth muscle contraction, particularly in arteries.

  • Contrast calcium regulation in striated and smooth muscle.

Structural Components in Smooth Muscle

• Layers of Blood Vessel

  • Intima: Contains endothelium and a basement membrane.

  • Media: Composed of smooth muscle cells, and contains collagen and elastin.

  • Adventitia: The outermost layer containing more collagen and fibroblasts.

Actin and Myosin in Cells

• Role in Cell Movement:

  • Stress Fibers: Actin filaments form stress fibers that contribute to cell shape and movement.

  • Fibroblast Dynamics: Different organizations of actin impact cell motility and shape.

Motor Proteins Overview

• Motor Proteins:

  • Kinesin-I and Dynein for transport; Myosin for muscle contraction.

  • Functionality relies on domains for filament binding, cargo binding, and ATP-dependent motion.

Myosin Structure and Function

• Myosin Heads:

  • Comprised of S1 fragment, tail, and ATP binding site.

  • Essential for generating contractile force in muscle fibers.

Calcium and Muscle Contraction

• Calcium Regulation:

  • Low calcium leads to muscle relaxation while high calcium activates contraction via pathways involving myosin light chain kinase (MLCK).

  • Calcium binds to calmodulin, which activates MLCK, leading to phosphorylation of myosin light chains.

Smooth Muscle Contraction Mechanism

• Angiotensin II Mechanism:

  • Activates vasoconstriction through the activation of PLC-IP3-Ca++ pathways.

  • Myosin light chains are phosphorylated leading to contraction.

Mechanisms of Smooth Muscle Contraction

• Contractile Regulation:

  • Involves caldesmon for assembly and contraction regulation of smooth muscle filaments.

  • Works in conjunction with tropomyosin and actin.

Angiogenesis and Vascularization

• Purpose of Angiogenesis:

  • Growth of tissue, repair, and inflammation necessitates development of new blood vessels.

  • Pericytes play crucial roles in formation and stabilization of capillaries during angiogenesis.

Cancer Biology Learning Objectives

• Cancer Topics to Study:

  • Evolutionary context for cancer progression.

  • Differences in environmental vs genetic causes of cancer.

  • The role of microenvironments and adhesion in tumor growth and metastasis.

Mechanisms of Tumorigenesis

• Tumor Initiators and Promoters:

  • Understand distinct roles that mutations play in initiating cancer and promoting its progression.

  • Knowledge of oncogenes versus tumor suppressor genes and their functions in regulating cell growth.

Additional Key Points

• Resistance Arteries: Control blood flow through smooth muscle contractions and responses to neural signals.

• Role of Curing Mutagenic Factors: Ames test for carcinogens and impact of chemical exposure on cancer onset.