ChannelsLecture

Line tension applied tension dissecting the free

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Line Tension & Applied Tension
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Dissecting the Free Energy: Dissecting the Free Energy: Hydrophobic Mismatch Hydrophobic Mismatch Hydrophobic mismatch Can tune the hydrophobic mismatch two ways: change the lipids or mutate the protein.
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An Effective Potential For Channel An Effective Potential For Channel Opening Opening Elastic deformation of the membrane is induced by channel. Thickness mismatch leads to a line tension which works against applied tension Effective potential analogous to a nucleation problem. Effective potential for channel radius Applied tension
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Experimental Predictions Experimental Predictions Critical tension depends upon lipid length. Curvature inducing lipids can change the sign of the effective line tension – stabilizing open state. Amino acid substitutions that tune the hydrophobic width of the channel alter gating tension in a systematic fashion.
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The Curious Case of Voltage Gating The Curious Case of Voltage Gating The idea: ion channels (such as for K) are gated by voltage. Structural biologists have made huge progress, but their successes have left a wake of paradoxes. RP opinion: careless in treatment of membrane! Membrane mechanics distinguishes them. (Mackinnon et al .)
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Flirting with a Simple Model of Voltage Flirting with a Simple Model of Voltage Gating Gating Same logic – write free energy which reflects response of channel AND surrounding membrane. How gating depends upon voltage, tension (!), lipid character, etc… Testable – SMB bring it on! Two models have different consequences.
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Ear Structure and Function: Ion Ear Structure and Function: Ion Channel Gating Channel Gating (Cochlear function.) Collective response of multiple detectors driving multiple channels.
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Richness of Dynamics: Adaptation Richness of Dynamics: Adaptation (Sukharev et al .) Hair cells exhibit nonlinear response – they adapt to stimulus. Relevant molecular participants are as yet unknown. (Muller and Littlewood-Evans)
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