Stimulated secretion in endocrine cells and neuronal synapses causes a rise in endocytosis rates to recover the added membrane. The endocytic process involves the mechanical deformation of the membrane to produce an invagination. Studies of osmotic swelling effects on endocytosis indicate that the increased surface tension is tightly correlated to a significant decrease of endocytosis. When rat basophilic leukemia (RBL) cells are stimulated to secrete, there is a dramatic drop in the membrane tension and only small changes in membrane bending stiffness. Neither the shape change that normally accompanies secretion nor the binding of ligand without secretion causes a drop in tension. Further, tension decreases within 6 s, preceding shape change and measurable changes in endocytosis. After secretion stops, tension recovers. On the basis of these results we suggest that the physical parameter of membrane tension is a major regulator of endocytic rate in RBL cells. Low tensions would stimulate endocytosis and high tensions would stall the endocytic machinery.

The amoeboid myosin I's are required for cellular cortical functions such as pseudopod formation and macropinocytosis, as demonstrated by the finding that Dictyostelium cells overexpressing or lacking one or more of these actin-based motors are defective in these processes. Defects in these processes are concomitant with changes in the actin-filled cortex of various Dictyostelium myosin I mutants. Given that the amoeboid myosin I's possess both actin- and membrane-binding domains, the mutant phenotypes could be due to alterations in the generation and/or regulation of cell cortical tension. This has been directly tested by analyzing mutant Dictyostelium that either lacks or overexpresses various myosin I's, using micropipette aspiration techniques. Dictyostelium cells lacking only one myosin I have normal levels of cortical tension. However, myosin I double mutants have significantly reduced (50%) cortical tension, and those that mildly overexpress an amoeboid myosin I exhibit increased cortical tension. Treatment of either type of mutant with the lectin concanavalin A (ConA) that cross-links surface receptors results in significant increases in cortical tension, suggesting that the contractile activity of these myosin I's is not controlled by this stimulus. These results demonstrate that myosin I's work cooperatively to contribute substantially to the generation of resting cortical tension that is required for efficient cell migration and macropinocytosis.

The plasma membrane of most cells is drawn tightly over the cytoskeleton of the cell, resulting in a significant tension being developed in the membrane. The tension in the membrane can be calculated fi-om the force required to separate it ffom the cytoskeleton; and the force itself can be measured rapidly by using laser tweezers. Recent observations indicate that decreasing membrane tension stimulates endocytosis and increasing tension stimulates secretion. Thus, membrane tension provides a simple physical mechanism to control the area of the plasma membrane. Here, we speculate that tension is a global parameter that the cell uses to control physically plasma membrane dynamics, cell shape and cell motility.

Membrane tension has been proposed to be important in regulating cell functions such as endocytosis and cell motility. The apparent membrane tension has been calculated from tether forces measured with laser tweezers. Both membrane-cytoskeleton adhesion and membrane tension contribute to the tether force. Separation of the plasma membrane from the cytoskeleton occurs in membrane blebs, which could remove the membrane-cytoskeleton adhesion term. In renal epithelial cells, tether forces are significantly lower on blebs than on membranes that are supported by cytoskeleton. Furthermore, the tether forces are equal on apical and basolateral blebs. In contrast, tether forces from membranes supported by the cytoskeleton are greater in apical than in basolateral regions, which is consistent with the greater apparent cytoskeletal density in the apical region. We suggest that the tether force on blebs primarily contains only the membrane tension term and that the membrane tension may be uniform over the cell surface. Additional support for this hypothesis comes from observations of melanoma cells that spontaneously bleb. In melanoma cells, tether forces on blebs are proportional to the radius of the bleb, and as large blebs form, there are spikes in the tether force in other cell regions. We suggest that an internal osmotic pressure inflates the blebs, and the pressure calculated from the Law of Laplace is similar to independent measurements of intracellular pressures. When the membrane tension term is subtracted from the apparent membrane tension over the cytoskeleton, the membrane-cytoskeleton adhesion term can be estimated. In both cell systems, membranecytoskeleton adhesion was the major factor in generating the tether force.

When neurons undergo dramatic shape and volume changes, how is surface area adjusted appropriately? The membrane tension hypothesis-namely that high tensions favor recruitment of membrane to the surface whereas low tensions favor retrieval-provides a simple conceptual framework for surface area homeostasis. With membrane tension and area in a feedback loop, tension extremes may be averted even during excessive mechanical load variations. We tested this by measuring apparent membrane tension of swelling and shrinking Lymnaea neurons. With hypotonic medium (50%), tension that was calculated from membrane tether forces increased from 0.04 to as much as 0.4 mN/m, although at steady state, swollen-cell tension (0.12 mN/m) exceeded controls only threefold. On reshrinking in isotonic medium, tension reduced to 0.02 mN/m, and at the substratum, membrane invaginated, creating transient vacuolelike dilations. Swelling increased membrane tension with or without BAPTA chelating ytoplasmic Ca2+, but with BAPTA, unmeasurably large (although not lytic) tension surges occurred in approximately two-thirds of neurons. Furthermore, in unarborized neurons voltage-clamped by perforated-patch in 50% medium, membrane capacitance increased 8%, which is indicative of increasing membrane area. The relatively damped swelling–tension responses of Lymnaea neurons (no BAPTA) were consistent with feedback regulation. BAPTA did not alter resting membrane tension, but the large surges during swelling of BAPTA-loaded neurons demonstrated that 50% medium was inherently treacherous and that tension regulation was impaired by subnormal cytoplasmic [Ca2+]. However, neurons did survive tension surges in the absence of Ca2+ signaling. The mechanism to avoid hightension rupture may be the direct tension-driven recruitment of membrane stores.