Hyperthermia effects on the cytoskeleton and on cell morphology.

Human erythrocyte ghost membranes undergo five thermal transitions at temperatures between 50 and 75 degrees C. Spontaneous fragmentation of whole cells occurs at 50 degrees C, a transition temperature which has been associated with denaturation of the cytoskeletal protein spectrin. Haemolysis occurs at 65 degrees C and microvesiculation of the resulting ghost membrane is seen at temperatures in excess of 70 degrees C. The cell fragmentation develops through spatially periodic growth of surface waves on the erythrocyte membrane. The interfacial instability associated with the surface wave growth arises from thermal impairment of the stabilizing function of spectrin. Interfacial instability is also associated with the beading pattern which arises when long processes drawn mechanically from erythrocytes are heated. Similar beading of cell processes is a feature of many cytoskeleton-weakening agents acting on nonerythroid cells. The complexities of the cytoskeletons of eucaryotic cells including structure, composition and interaction of cytoskeletal microfilaments, microtubules and intermediate filaments, both with each other and with the cell membrane, are outlined. Attention is drawn to the importance of the function of proteins which interact with the cytoskeletal elements and to the influence of calcium concentration on those proteins. Actin monomers are denatured (and are no longer polymerizable) at temperatures a few degrees above the growth temperature of the cell source of the actins. Actin in the filament form requires much higher denaturation temperatures. This greater thermal lability of actin monomers would be expected to result (because of treadmilling in microfilaments) in a gradual depolymerization of the filaments. Depolymerization of microtubules occurs at temperatures close to the cell growth temperature and may be dependent on a thermal effect on microtubule-associated proteins. The response of spread interphase mammalian cells to temperatures around 43 degrees C includes central retraction of membrane, loss of microvilli, concentration of organelles in a juxtanuclear position, rounding up of the cell, retention of contact with the substratum by processes which are sometimes beaded and blebbing of the cell membrane. The morphological effects of heat are compared here with those of cytochalasin, colcemid and a number of morphology modifying agents. Blebbing of membrane is a fairly general response of cells to stress. Proteins in blebs diffuse as if released from a lateral constraint. Moderate heating has been shown to cause cortical microfilament separation from the plasma membrane.(ABSTRACT TRUNCATED AT 400 WORDS)