Podcast
Questions and Answers
What is chemotaxis primarily characterized by?
What is chemotaxis primarily characterized by?
What are the molecules called that attract cells toward them?
What are the molecules called that attract cells toward them?
Which protein is crucial for the generation of polarity in migrating cells?
Which protein is crucial for the generation of polarity in migrating cells?
Which complex do WASP/WAVE proteins primarily act on?
Which complex do WASP/WAVE proteins primarily act on?
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What role does PTEN play in cell migration?
What role does PTEN play in cell migration?
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What process is necessary for the stabilization of protrusions during cell migration?
What process is necessary for the stabilization of protrusions during cell migration?
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Which signaling pathway is involved in integrin activation?
Which signaling pathway is involved in integrin activation?
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What happens to adhesions at the rear of the cell during migration?
What happens to adhesions at the rear of the cell during migration?
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What role does ATP play in muscle contraction?
What role does ATP play in muscle contraction?
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Which process primarily drives the force generation in muscle contraction?
Which process primarily drives the force generation in muscle contraction?
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What cellular event occurs first during cell crawling?
What cellular event occurs first during cell crawling?
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How do RhoA and Rac work together in directional movement?
How do RhoA and Rac work together in directional movement?
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What happens during muscle relaxation?
What happens during muscle relaxation?
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What is one of the distinct events involved in cell crawling?
What is one of the distinct events involved in cell crawling?
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In the context of angiogenesis, what is the significance of pericytes?
In the context of angiogenesis, what is the significance of pericytes?
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What is one of the key signaling processes in endothelial tip growth during angiogenesis?
What is one of the key signaling processes in endothelial tip growth during angiogenesis?
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What happens to the sarcomere when the muscle contracts?
What happens to the sarcomere when the muscle contracts?
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What are the structures in smooth muscle that serve a similar purpose to sarcomeres in striated muscle?
What are the structures in smooth muscle that serve a similar purpose to sarcomeres in striated muscle?
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Which protein is responsible for initiating the contraction process in striated muscles through calcium binding?
Which protein is responsible for initiating the contraction process in striated muscles through calcium binding?
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Why does dynamic instability or treadmilling not occur in actin filaments of striated muscle?
Why does dynamic instability or treadmilling not occur in actin filaments of striated muscle?
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What causes the myosin heads to remain attached to actin filaments during rigor mortis?
What causes the myosin heads to remain attached to actin filaments during rigor mortis?
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What effect does high calcium concentration have in smooth muscle contraction?
What effect does high calcium concentration have in smooth muscle contraction?
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In what form does myosin exist in its functional state within both smooth and striated muscle?
In what form does myosin exist in its functional state within both smooth and striated muscle?
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How does phosphorylation of the myosin light chain affect muscle contraction in smooth muscle?
How does phosphorylation of the myosin light chain affect muscle contraction in smooth muscle?
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What is the primary role of myosin in muscle cells?
What is the primary role of myosin in muscle cells?
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How do kinesin and dynein differ from myosin?
How do kinesin and dynein differ from myosin?
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Which component of myosin changes upon activation?
Which component of myosin changes upon activation?
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What molecular mechanism generates force on actin filaments?
What molecular mechanism generates force on actin filaments?
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What type of microscopy can be used to measure forces on single molecules?
What type of microscopy can be used to measure forces on single molecules?
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What is a structural feature unique to myosin?
What is a structural feature unique to myosin?
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What method is employed to study myosin movement with fluorescent actin?
What method is employed to study myosin movement with fluorescent actin?
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Which statement correctly contrasts striated and smooth muscle calcium regulation?
Which statement correctly contrasts striated and smooth muscle calcium regulation?
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What are the two essential components required for tumor growth?
What are the two essential components required for tumor growth?
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How do tumors ensure they have sufficient nutrients?
How do tumors ensure they have sufficient nutrients?
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What factors influence whether cancer cells can metastasize to a specific location in the body?
What factors influence whether cancer cells can metastasize to a specific location in the body?
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What does the Ames test measure regarding a compound's effects?
What does the Ames test measure regarding a compound's effects?
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How is carcinogenic potency defined?
How is carcinogenic potency defined?
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What critical function do signals secreted by hypoxic tumor cells serve?
What critical function do signals secreted by hypoxic tumor cells serve?
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In the context of the Ames test, what does mutagenic potency refer to?
In the context of the Ames test, what does mutagenic potency refer to?
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What is a potential outcome of artificially induced microevolution in cancer research?
What is a potential outcome of artificially induced microevolution in cancer research?
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What is the primary function of optical tweezers in studying myosin movement?
What is the primary function of optical tweezers in studying myosin movement?
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How does fluorescent spot tracking contribute to understanding myosin movement?
How does fluorescent spot tracking contribute to understanding myosin movement?
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What does a graph showing a 72 µm distance indicate about myosin's movement?
What does a graph showing a 72 µm distance indicate about myosin's movement?
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What are the limitations of using fluorescent spot tracking for myosin analysis?
What are the limitations of using fluorescent spot tracking for myosin analysis?
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What is the advantage of atomic force microscopy in studying myosin?
What is the advantage of atomic force microscopy in studying myosin?
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Which statement best describes the method of optical tweezers?
Which statement best describes the method of optical tweezers?
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In the context of myosin movement, what does a power stroke refer to?
In the context of myosin movement, what does a power stroke refer to?
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What is the significance of measuring displacement with nanometer and piconewton accuracy?
What is the significance of measuring displacement with nanometer and piconewton accuracy?
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Study Notes
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
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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.
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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.
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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).
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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.
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Optical Tweezers: Measure force generated from a single myosin contraction; uses beads suspended on an actin filament with myosin to measure displacement and force.
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Fluorescent Spot Tracking: Measures distance of a myosin swing based on myosin tails being labeled and tracked down a microfilament.
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Atomic Force Microscopy: Visualizes myosin movement in real time, using vibrating needles across the surface of a protein.
November 18th - Smooth Muscle Function
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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.
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Force generation: Requires interaction of actin and myosin. Actin and myosin must be in proximity to undergo conformational changes and interact.
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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.
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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.
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Energy is required: Sufficient ATP fuels cross bridge cycling during contraction. ATP is needed for phosphorylation/dephosphorylation for filament assembly and disassembly.
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Signal Detection: Stimuli like neurotransmitters open ion channels, increasing intracellular [Ca2+], RhoA signaling.
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Energy Flow: ATP powers myosin activation, filament assembly, and cross-bridge cycling.
November 20th - Crawling Motility and Angiogenesis
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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
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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
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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
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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.
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Unicellular functions: in multicellular cancers can be reactivated and upregulated due to mutation; multicellular regulators of these unicellular functions are downregulated.
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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.
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Contact Inhibition: Mechanism of cell division regulation; mutation in this mechanism permits continuous cell division and stacking of cells.
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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.
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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.
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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
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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.
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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).
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Retinoblastoma: Hereditary vs. Nonhereditary modes of RB transmission and mutation; implications for the RB gene in uncontrolled cell division causing tumor formation.
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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.
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Additional points concerning the various aspects of cancer.
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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.