Cell Biology Quiz: Chemotaxis and Migration

Cells and Cell Systems Review

• Table of Contents: Provides lecture topics and dates for the course. Topics include cytoskeleton for arteries (November 15th), smooth muscle function (November 18th), crawling motility and angiogenesis (November 20th), Cancer lecture 1 (November 22nd), Cancer lecture 2 (December 4th), and Cancer lecture 3 (December 6th).

November 15th - Cytoskeleton for Arteries

• Learning Objectives: Students should be able to explain how force is generated on actin filaments, describe optical methods of measuring forces on single molecules, and interpret data from these methods. Also describe actin/myosin interactions in striated muscle. Apply principles from striated muscle to smooth muscle in arteries, and contrast how calcium regulates striated and smooth muscle.

• Motor Proteins: Motor proteins move cargo along filaments; myosin associates with microfilaments and kinesin/dynein associates with microtubules. Similarities between kinesin/dynein and myosin include 2 force-generating heads and filament binding. Dynein/kinesin and myosin also possess tails and light chains.

• Myosin: Myosin proteins pull on actin filaments in cells to generate contractile force. Different myosin types have different functions but similar structure with a force-generating ATP-binding domain. Structure features include a coiled coil tail region that connects the filament and cargo domains, and regulatory subunits that change with myosin activation. Several types of myosin are mentioned (Myosin II, Myosin I, Myosin V, Myosin VI).

• Studying Myosin Movement: Biochemistry method, fixing S1 fragments of myosin to a slide with fluorescent actin and adding ATP. Optical methods include optical tweezers, fluorescent spot tracking, and atomic force microscopy.

• Optical Tweezers: Measure force generated from a single myosin contraction; uses beads suspended on an actin filament with myosin to measure displacement and force.

• Fluorescent Spot Tracking: Measures distance of a myosin swing based on myosin tails being labeled and tracked down a microfilament.

• Atomic Force Microscopy: Visualizes myosin movement in real time, using vibrating needles across the surface of a protein.

November 18th - Smooth Muscle Function

• Learning Objectives: Describe assembly and disassembly of contractile units in smooth muscle; describe how caldesmon regulates contraction in smooth muscle; dissect signaling process to identify key elements controlling smooth muscle contraction, and predict what signals cause opening or closing of capillary beds.

• Force generation: Requires interaction of actin and myosin. Actin and myosin must be in proximity to undergo conformational changes and interact.

• Molecular Conformation: Proteins like myosin & regulatory enzymes operate by switching between active and inactive conformations. Calcium ions act a signal regulating calmodulin, MLCK, and MLCP. Phosphorylation of the myosin light chain (MLC) is essential for altering myosin structure allowing its interaction with actin.

• Stability and change: Actin filaments require stabilization by proteins like tropomyosin for structural integrity. Myosin filaments self-assemble into a functional form, dependent on the phosphorylation state of MLC, and its hydrolysis.

• Energy is required: Sufficient ATP fuels cross bridge cycling during contraction. ATP is needed for phosphorylation/dephosphorylation for filament assembly and disassembly.

• Signal Detection: Stimuli like neurotransmitters open ion channels, increasing intracellular [Ca2+], RhoA signaling.

• Energy Flow: ATP powers myosin activation, filament assembly, and cross-bridge cycling.

November 20th - Crawling Motility and Angiogenesis

• Learning Objectives: Contrast force generation in crawling motility to smooth muscle contraction, describe how Rac and Rho collaborate to create directional movement; describe roles of pericytes in blood vessels and angiogenesis; contrast pericyte function to endothelial tip growth in vessel formation, and compare/contrast signaling processes (HIF1, VGF, Delta/Notch) in tip growth

• Crawling cells (movement): Involves the following key events to crawl: . Extension of the protrusion at the leading edge; attachment to substrate; tension generation that pulls the cell forward; release of trailing edge attachments and retraction

• Cell protrusion (development): . Types of Protrusion: Sheet (lamellipodium), thin projections (Filopodia), . Forward construction of protrusions controlled by Arp2/3 depedent branching. Polymerized actin that cells produce regulated by small GTPases (Rho, Rac, Cdc42). Rac promotes lamellipodia, while Cdc42 promotes filopodia.

. Cell attachment (development): . Integrins on outside of the cell attach to extracellular matrix proteins. Integrins connected to actin filaments form focal adhesions.

December 4th - Second Cancer Lecture

• Cancer Cell Evolution: Mutations create new traits; environmental constraints select for mutations allowing for different lineages with different fitness levels; occurs because cancer cells divide rapidly.

• Unicellular functions: in multicellular cancers can be reactivated and upregulated due to mutation; multicellular regulators of these unicellular functions are downregulated.

• Normal versus Tumor Growth: Graph of normal cell growth versus tumor growth, showing shedding of dead cells versus cell division/migration and difference in basal layers.

• Contact Inhibition: Mechanism of cell division regulation; mutation in this mechanism permits continuous cell division and stacking of cells.

• Tumor Growth Phases: two required phases for tumor growth including: mutation and proliferation inducing irritant. Two general types of tumor growth include increased division and decreased cell death.

• Vascularization: Tumors must establish a vasculature for nutrient uptake and expansion; tumor cells secrete hormones/signaling to recruit and form new vasculature when exposed to low oxygen.

• Metastasis: Cancer cells invade the bloodstream and deposit/metastasize elsewhere in the body. Factors like cell origin influence how cells respond and their ability to move.

December 6th - Third Cancer Lecture

• Crude method for finding oncogenes: Combines cancer and normal cells to identify working tumor suppressor genes versus oncogenes . Hybrid cells have both normal and cancer cell DNA creating working tumor suppressor genes to control oncogenes. . Following subsequent divisions, some chromosomes are lost, resulting in enhanced protein activity (oncogene) but without suppressor brakes.

• Human Papilloma Virus: Activation of the p53 pathway as a response to DNA damage; HPV proteins E6 and E7 ubiquitinate p53 and bind to Rb respectively (thus inhibiting apoptosis and halting cell division).

• Retinoblastoma: Hereditary vs. Nonhereditary modes of RB transmission and mutation; implications for the RB gene in uncontrolled cell division causing tumor formation.

• Genetic details of Hereditary versus Non-Hereditary RB: Inheriting an RB mutation implies that there is mutation in one copy of the RB gene present in all body cells; a second mutation in the other RB copy occurs in one or more retina cells. Without this second mutation the RB gene function remains intact. This is not the case when the mutation is caused by non hereditary ways. The copy is lost during any subsequent division of cells.

• Additional points concerning the various aspects of cancer.

Test your knowledge on the mechanisms of chemotaxis and cell migration with this quiz. Explore key concepts such as signaling pathways, protein functions, and the role of molecules in guiding cells. Ideal for students studying advanced cell biology topics.