Proteins integral lateral diffusion

Alkyl chain heterogeneities cause cell membrane bilayers to remain in the fluid state over a broad temperature range. This permits rapid lateral diffusion of membrane lipids and proteins within the plane of the bilayer. The lateral diffusion rate for an unconstrained phospholipid in a bilayer is of the order of 1 mm2 s 1 an integral membrane protein such as rhodopsin would diffuse 40nm2 s 1. 

Fig. 2.19 Diagram of the plasma membrane showing its integral proteins (fluid mosaic model) (adapted from S.J. Singer et af, 1972 and H. Knufermann, 1976). 1 external aqueous milieu, 2 internal aqueous milieu, 3 fracture plane of the apolar membrane layer, 4 externally orientated intrinsic protein (ectoprotein), 5 internally orientated intrinsic protein (endoprotein), 6 external extrinsic protein, 7 internal intrinsic protein, 8, 9 membrane-penetrating proteins with hydrophobic interactions in the inside of the membrane (P = polar region), 10 membrane pervaded by glycoprotein with sugar residues (, 11 lateral diffusion (A) and flip-flop (B), 12 hydrophilic region (A) and hydrophobic region (B) of the bilayer membrane...

Experimental interest lies in the value of q that depends on the applied concentration, that is, where q =/(c), which thus describes the isotherm-of the adsorbate. Application of protein solution to the column produced an effluent profile of the type shown in Figure 5. The amount of protein adsorbed may be calculated by integrating the area between the void volume and the actual effluent profile (lateral diffusion, DM, does not modify the integrated area). A series of runs using different cG values thus establishes a dynamic isotherm. 

The difference in diffusion rates is due primarily to the difference in mass between phospholipids, which have a molecular weight of approximately 800, and proteins, which have a molecular weight greater than 10,000. In addition, integral membrane proteins may associate with peripheral proteins, which would further decrease their lateral diffusion. 

For cell membranes to be effective permeability barriers, they must be flexible and allow relatively free motion of proteins that are embedded in or linked to them. Integral membrane proteins often diffuse laterally, and many receptor-mediated solute-uptake pathways involve endocytosis that entails phospholipid rearrangement in the membrane. Hormone secretion and other protein trafficking processes involve exo-cytosis and it is usual for membrane vesicles to fuse with each other in a process that also involves the lateral diffusion of membrane constituents. The activity of some receptors is strongly linked to the extent of fluidity of the membrane around them. 

Just how fast can proteins move in a biological membrane Many membrane proteins can move laterally across a membrane at a rate of a few microns per minute. On the other hand, some integral membrane proteins are much more restricted in their lateral movement, with diffusion rates of about 10 nm/sec or even slower. These latter proteins are often found to be anchored to the cytoskeleton (Chapter 17), a complex latticelike structure that maintains the cell s shape and assists in the controlled movement of various substances through the ceil. 

The fluidity of lipid bilayers permits dynamic interactions among membrane proteins. For example, the interactions of a neurotransmitter or hormone with its receptor can dissociate a transducer protein, which in turn will diffuse to interact with other effector proteins (Ch. 19). A given effector protein, such as adenylyl cyclase, may respond differently to different receptors because of mediation by different transducers. These dynamic interactions require rapid protein diffusion within the plane of the membrane bilayer. Receptor occupation can initiate extensive redistribution of membrane proteins, as exemplified by the clustering of membrane antigens consequent to binding bivalent antibodies [8]. In contrast to these examples of lateral mobility, the surface distribution of integral membrane proteins can be fixed by interactions with other proteins. Membranes may also be partitioned into local spatial domains consisting of networks... 

The fluid-mosaic model for biological membranes as envisioned by Singer and Nicolson. Integral membrane proteins are embedded in the lipid bilayer peripheral proteins are attached more loosely to protruding regions of the integral proteins. The proteins are free to diffuse laterally or to rotate about an axis perpendicular to the plane of the membrane. For further information, see S. J. Singer and G. L. Nicolson, The fluid mosaic model of the structure of cell membranes, Science 175 720, 1972. 

Phospholipid molecules in the plasma membrane diffuse rapidly enough to go from one end of an average-sized animal cell to the other in a few minutes. In a bacterial cell, such a trip would take only a few seconds. Integral membrane proteins move more slowly than phospholipids, as we expect in view of their greater mass. Diffusion of membrane proteins plays essential roles in many biochemical processes, including the cellular uptake of lipoproteins (chapter 18), responses of cells to hormones (chapter 24), immunological reactions (supplement 3), vision (supplement 2), and the transport of nutrients and ions. As we see in a later section, however, some membrane proteins cannot move about rapidly because they are attached to cytoskeletal scaffolds. 

Integral proteins are usually free to move in the plane of the bilayer by lateral and rotational movement, but are not able to flip from one side of the membrane to the other (transverse movement). Immunofluorescence microscopy may be used to follow the movement of two proteins from different cells following fusion of the cells to form a hybrid heterokaryon. Immediately after fusion the two integral proteins are found segregated at either end of the heterokaryon but with time diffuse to all areas of the cell surface. The distribution of integral proteins within the membrane can be studied by electron microscopy using the freeze-fracture technique in which membranes are fractured along the interface between the inner and outer leaflets. 

On the basis of the dynamic properties of proteins in membranes, S. Jonathan Singer and Garth Nicolson proposed the concept of a fluid mosaic model for the overall organization of biological membranes in 1972 (Figure 1230). The essence of their model is that membranes are two-dimensional solutions of oriented lipids and globular proteins. The lipid bilayer has a dual role it is both a solvent for integral membrane proteins and a permeability barrier. Membrane proteins are free to diffuse laterally in the lipid matrix unless restricted by special interactions. 

In a membrane, an integral membrane protein diffuses laterally an average distance of 4 X 10 m in 1 minute, whereas a phospholipid molecule diffuses an average distance of 2 pm in 1 second. 

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