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Forces in a biological context

By Jonathan W. Armond


Theoretical modelling of the microtubule-Dam1-ring force generation mechanism\ud and the pulling of tubes from surface-supported lipid bilayers are presented and\ud discussed. Atomic force microscopy (AFM) force data of tube pulling experiments\ud is analysed and compared with theoretical predictions.\ud Featurescommonto recent computational models are simplified and examined\ud independently where possible. In particular, the steric confinement of the Dam1\ud ring on a microtubule (MT) by protofilaments (PFs), the powerstroke produced by\ud curling PFs, the depolymerisation of the MT, and the binding attraction between\ud Dam1 and the MT are modelled. Model parameters are fitted to data. Functional\ud force generation is equally demonstrated when attachment is maintained by steric\ud confinement alone (protofilament model) or by a binding attraction alone (binding\ud model). Moreover, parameters amenable to experimental modification are shown\ud to induce differences between the protofilament model and the binding model.\ud Changing the depolymerisation rate of MTs, the diffusion coefficient of the Dam1\ud ring, or applying an oscillating load force will allow discrimination of these two\ud different mechanisms of force generation and kinetochore attachment.\ud A previously described theoretical model of pulling lipid bilayer tubes from\ud vesicles is modified for the case of pulling tubes from surface-supported lipid\ud bilayers. A shape equation for axisymmetric membranes is derived variationally\ud and solved numerically for zero pressure. Free energy profiles and force curves\ud are calculated for various AFM probe sizes and compared to experimental data\ud where a ground flat AFM probe is used to pull tubes from surface-supported lipid\ud bilayers. The predicted force curves partially fit the experimental data, although\ud not at short distances, and estimates of the bilayer surface tension are given.\ud Pressure and volume profiles are calculated for the extension of the model to the\ud nonzero pressure case

Topics: QA, QH
OAI identifier: oai:wrap.warwick.ac.uk:4480

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