page_title: Membrane models
section_title: Henderson and Unwin's membrane theory
hierarchical_section_title: Membrane models / Henderson and Unwin's membrane theory
caption_attribution_description: English: Created using PyMol and a homology model of the TRPV1 ion channel based on a homology model published in Brauchi S, Orta G, Mascayano C, Salazar M, Raddatz N, Urbina H, Rosenmann E, Gonzalez-Nilo F, Latorre R (June 2007). "Dissection of the components for PIP2 activation and thermosensation in TRP channels". Proceedings of the National Academy of Sciences of the United States of America 104 (24): 10246–51. DOI:10.1073/pnas.0703420104. PMID 17548815. PMC: 1891241.
context_page_description: Before the emergence of electron microscopy in the 1950s, scientists did not know the structure of a cell membrane or what its components were; biologists and other researchers used indirect evidence to identify membranes before they could actually be visualized. Specifically, it was through the models of Overton, Langmuir, Gorter and Grendel, and Davson and Danielli, that it was deduced that membranes have lipids, proteins, and a bilayer. The advent of the electron microscope, the findings of J. David Robertson, the proposal of Singer and Nicolson, and additional work of Unwin and Henderson all contributed to the development of the modern membrane model. However, understanding of past membrane models elucidates present-day perception of membrane characteristics. Following intense experimental research, the membrane models of the preceding century gave way to the fluid mosaic model that is accepted today.
context_section_description: Henderson and Unwin have studied the purple membrane by electron microscopy, using a method for determining the projected structures of unstained crystalline specimens. By applying the method to tilted specimens, and using the principles put forward by DeRosier and Klug for the combination of such two-dimensional views, they obtained a 3-dimensional map of the membrane at 7 Å resolution. The map reveals the location of the protein and lipid components, the arrangement of the polypeptide chains within each protein molecule, and the relationship of the protein molecules in the lattice.
  High-resolution micrographs of crystalline arrays of membrane proteins, taken at a low dose of electrons to minimize radiation damage, have been exploited to determine the three-dimensional structure by a Fourier transform. 
  Recent studies on negatively stained rat hepatocyte gap junctions subjected to 3-dimensional Fourier reconstructions (of low-dose electron micrographs) indicate that the six protein sub-units are arranged in a cylinder slightly tilted tangentially, enclosing a channel 2 nm wide at the extracellular region. The dimensions of the channel within the membrane were narrower but could not be resolved (Unwin and Zampighi, 1980). A small radical movement of the sub-units at the cytoplasmic ends could reduce the sub-unit inclination tangential to six-fold axis and close the channel.
  Further details of the molecular organization should emerge as more methods of preparation become available, so that high-resolution 3-dimensional images comparable to the purple membranes are obtained. By using ingenious procedures for the analysis of periodic arrays of biological macromolecules, in which data from low-dose electron images and diffraction patterns were combined, Henderson and Unwin (1975) reconstructed a three-dimensional image of purple membranes at 0.7 nm resolution. Glucose embedding was employed to alleviate dehydration damage and low doses (< 0.5 e/A*) to reduce the irradiation damage. The electron micrographs of unstained membranes were recorded such that the only source of contrast was a weak phase contrast induced by defocusing.
  In their experiment, Unwin and Henderson found that protein extends to both sides of the lipid bi-layer and is composed of seven α-helices packed about 1–1.2 nm apart, 3.5–4.0 nm in length, running perpendicular to the plane of membrane.  The molecules are organized around a 3-fold axis with a 2 nm-wide space at the center that is filled with lipids. This elegant work represents the most significant step forward thus far, as it has for the first time provided us with the structure of an integral membrane protein in situ.
  The availability of the amino acid sequence, together with information about the electron scattering density from the work of Henderson and Unwin, has stimulated model-building efforts (Engleman et al., 1980) to fit the bacteriorhodopsin sequence information into a series of α-helical segments.
caption: Transient receptor potential cation channel subfamily V member 1 (TRPV1). Ion channels are integral membrane proteins of great importance for living organisms.
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