The importance of membrane mechanics in vesicle adhesion

Jin Nam, University of Massachusetts Amherst

Abstract

This thesis explores the effects of bilayer mechanics on the adhesion of biomimetic membranes and vesicles, establishing copolymer lamellae as versatile model membranes that more widely vary membrane mechanics and chemical functionalization than can be achieved using phospholipids. This new biomimetic system provides fundamental insight into cell adhesion, and motivates new design strategies for vesicles in applications such as targeted delivery.^ This study focused on the dynamic adhesion kinetics and spreading of vesicle pairs held in micropipettes at moderate tensions. The program employed two copolymers of different membrane stiffnesses, a graft copolymer of poly(dimethyl siloxane)-poly(ethylene oxide) [PDMS-PEO] and a diblock copolymer of poly(butadiene)-PEO [PBD-PEO]. The depletion-driven adhesion between pairs of these vesicles was studied, as was the avidin-biotin-driven adhesion between functionalized vesicles. This experimental grid therefore varied the membrane stiffness, adhesion strength, and point-wise versus laterally uniform application of adhesive forces.^ This study systematically demonstrated, for the first time, the activated nature of vesicle adhesion and spreading, with the bending cost of kink formation at the spreading front comprising a line tension that destabilizes adhesion nuclei. Despite modest differences between the bending moduli of phospholipid and stiffer copolymer vesicles, the effect was often sufficiently strong to prevent spreading, or at least produce a lag time prior to the onset of spreading. For instance, flexible membranes subject to depletion forces as small as 0.008 erg/cm² responded instantaneous to changes in membrane tension, achieving the equilibrium contact angle in less than a second. Stiff vesicles, however, never spread over a substrate vesicle or displayed an equilibrium contact angle, even when depletion forces were increased to 0.35 erg/cm ². Avidin-biotin functionalized flexible vesicles displayed a lag time prior to spreading while fully functionalized stiff vesicles never spread over substrate vesicles. Of note, in cases where spreading did not, or had not yet occurred, there was evidence for adhesion in a contact nucleus. For instance, avidin-biotin functionalized vesicles could not be separated, and unfunctionalized vesicles subject to depletion forces deformed momentarily upon separation.^ Estimates of the activation energy associated with spreading for depletion-driven adhesion were consistent with experimental observations, while a semi-quantitative treatment of avidin-biotin binding kinetics predicted the form of the concentration-dependence of the pre-spreading lag time. Once initiated, spreading kinetics were rapid and independent of membrane tension.^ These results find significance in the areas of fundamental membrane physics and in biology. As micropipette manipulation is becoming an increasingly popular tool for membrane characterization, the current thesis demonstrates that the approach to equilibrium, as measured through the contact angle, may be impeded by bending mechanics, rendering the Young's analysis of adhesion strength meaningless. The findings also suggest that in cell adhesion and processes involving sharp membrane curvature, such as endocytosis, membrane mechanics likely plays an important role in the dynamic mechanism.^

Subject Area

Polymer chemistry|Materials science

Recommended Citation

Nam, Jin, "The importance of membrane mechanics in vesicle adhesion" (2008). Doctoral Dissertations Available from Proquest. AAI3315515.
https://scholarworks.umass.edu/dissertations/AAI3315515

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