DIRECT MEASUREMENT OF FORCES BETWEEN MEMBRANES OF MACROMOLECULES

这个项目的主题是， 将告诉我们这些分子如何相互作用 形成活细胞的功能单位。 的结果 这些直接测量与以前的测量大不相同 期待 例如，我们已经了解到，在重要的 最后几个纳米分子接触，相互作用 是由连续变化的水的去除功所支配的 溶剂从它们的表面，磷脂双层之间 膜，这些重要的“水化力”是微妙的 对脂质成分的微小变化敏感 极性基团，在生物化学控制下的变化， 膜结构的形成。 我们最近不仅成功地测量了力与 分子的分离以及它们的热变化 在相互接近的过程中。 在1纳米范围之外， 直接水合排斥，似乎大分子移动或 通过分子碰撞的“空间”作用而产生排斥。 然而，这些碰撞从不涉及分子接触，而是 通过分子表面之间的长程作用力发生。 的 结果是一种互动形式，与任何 它被认为是分子组装的关键。 现在可以使用这些数据来了解测量的力如何作用在 比如说控制接触和融合的功能层面 膜的，如在分泌过程中，或决定包装 DNA或其他长分子，或扰乱重排， 影响跨膜“门控”的蛋白质结构 离子通道，甚至影响酶的活性， 功能取决于包装组件的特定形式。 我们 一直在对这些进程中的每一个进程开展工作。

The theme of this project is that actual measurement of forces between large molecules will teach us how these molecules interact to form the functioning units of a living cell. The results of these direct measurements are quite different from earlier expectation. For example, we have learned that in the important last few nanometers where molecules approach contact, interaction is dominated by a continuously varying work of removal of water solvent from their surfaces, between phospholipid bilayer membranes, these important "hydration forces" are exquisitely sensitive to very small changes ln the composition of the lipid polar groups, changes that are under the biochemical control after formation of the membrane structure. We have recently succeeded in measuring not only the force vs. separation of molecules but also the change in their thermal motion during mutual approach. Outside the 1 nanometer range of direct hydration repulsion it appears that macromolecules move or undulate to repel by the "steric" action of molecules colliding. However these collisions never involve molecular contact but rather occur through long-range forces between molecular surfaces. The result is a form of interaction qualitively different from any that has been assumed to be responsible for molecular assembly. One can now use these data to see how the measured forces act at the functional level of, say, controlling the contact and fusion of membranes as in a secretory process, or determining the packing of DNA or other long molecules, or perturbing the rearrangements of protein structure that effect the "gating" of trans-membrane ionic channels, or even affect the activity of enzymes whose function depends on particular forms of packing components. We have been carrying out work on each of these processes.