High pressure treatment of microbial cells and plant and animal tissues at 100-400 MPa solubilizes cellular compounds such as metals, amino acids, and proteins, permeates extra-cellular compounds such as salts into cells and tissues, and causes hemolysis. After the pressure treatment, electron microscopic observation of yeast cells and biochemical analysis of animal tissues reveal a significant membrane breakage of nuclei, lysosomes, and vacuoles in addition to light cell membrane and cell wall damage. To understand these observed phenomena at the molecular level, we studied functional and structural changes of the membrane-bound Na
+, K
+-ATPase under increasing high pressure (in situ observation), and reached an interesting conclusion that contact faces of lipid and membrane-penetrating protein surfaces are reversibly separated to produce tunnels or holes at 100-250 MPa, followed by disordered breakdown of the membrane system including protein denaturation at 300 MPa or higher. This conclusion is well supported by the phase transition of the lipid bilayer membrane.
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