Lecture notes – final week 11C. CYTOSKELETON: Connecting inside to outside Big picture #1: Cell survival depends on its environment Erythrocytes (red blood cells) and leukocytes (white blood cells) are unusual, in that they can survive in the circulation as individual cells, not connected to each other or anchored to extracellular matrix. For most cells, cell-cell cohesionand cell-matrix adhesion are required for survival ("anchorage dependence"). Cells that detach from the matrix and from each other undergo programmed cell death known as anoikis. For a cancer cell to metastasize, it needs mutations that allow it to escape anoikis. Big picture #2: Cells are not static, but can move through tissues Most images and measurements of cells and molecules are static. But cells are in a constant state of flux, moving around each other, sampling the environment and the signals it contains, and sometimes engaging in directed migration in a specific direction in response to those signals. Endothelial cells migrate towards cells that emit distress signals due to low-oxygen conditions. Macrophages and other immune cells migrate within tissues to capture pathogens. Cells that line the gut have a short lifespan, and new cells are continually being produced and migrating to the appropriate site to replace the dead cells. During development, neurons extend 'growth cones' to sense the environment and find their way – often across extremely large distances – to connect to other neurons or into the skeletal muscle or smooth muscle that they will control. There are many other examples, in development and in the adult. The cytoskeleton provides the cell the ability to move and sense its environment.All cells have filamentous proteins that give them shape and structure. There are three major filament types: microtubules, which you have learned previously are involved in cell division; intermediate filaments, of which there are many types, including keratins and lamins; and actinmicrofilaments, which are the thinnest of the three but are centrally involved in cellular morphology and migration. In chapter 16 of Alberts' Molecular Biology of the Cell, you will learn more about the assembly and disassembly of actin and tubulin filaments (Alberts page 912-913, reprinted next, are a good summary). We will focus on actin filaments and their ability to change cell shape. ACTIN FILAMENTS Filamentous actin polymer Globular actin unit (pink) Actin monomers (pink in the figure above) are known as 'G-Actin' (G = Globular). Note how many globular actin monomers bind to each other to form an ordered, very long protein polymer. This form of actin is known as 'F-Actin' (F = Filamentous). The monomers are each only 5.5 nanometers long, but the filaments can be extremely long, can branch and form networks, and can dynamically lengthen and shorten. Actin is the most abundant protein in nature and makes up 5% of the protein in human cells.