Proteins at Interfaces: Conformational Behavior and Wear

摘要

Proteins at interfaces play a major role in biomaterials and lab-on-a-chip devices. Protein interactions with the surface change their conformations and therefore their ability to bind to their respective ligands. Another major area of interest surrounding biomaterials and lab-on-a-chip devices is the prediction and prevention of wear. Wear is the progressive loss of material from an object caused by contact and relative movement of the contacting solid, liquid, or gas. It is estimated that wear costs 1% of the gross domestic product (approximately $150 billion for the US). With the emergence of drug-releasing implants and lab-on-the-chip devices, wear has also become a major concern in bio- and nano- technology. In our laboratory, we use microtubules (filamentous proteins) gliding on kinesin motor proteins as transporters in biosensors. This system, known as the motility assay, is ideal for studying how the conformation of kinesins impacts the gliding of microtubules and therefore the performance of the biosensor. The proposed studies seek to show that kinesins' geometry changes with their grafting density following De Gennes' scaling laws for flexible polymers (Chapter 2 , published in Langmuir as E.L.P. Dumont, H. Belmas, and H. Hess, Observing the mushroom-to-brush transition for kinesin proteins, 2013, 29 (49), 15142-15145) and that microtubules experience molecular wear due to their repeated interactions with kinesins (Chapter 3, under review for Nature Nanotechnology as E.L.P. Dumont and H. Hess, Molecular wear of microtubules propelled by surface-adhered kinesins). These two results permit the prediction of the lifetime of biosensors using kinesin-propelled microtubules (Chapter 4, to be submitted to Nano Letters as Y. Jeune-Smith, E.L.P. Dumont and H. Hess, Wear and breakage combine to mechanically degrade kinesin-powered molecular shuttles). I also discuss the importance of mechanical fatigue for molecular machine design (Chapter 5, published as H. Hess and E.L.P. Dumont, Fatigue Failure and Molecular Machine Design, Small, 7, 1619-1623, 2011). Finally, and it is unrelated to the previous chapters, I developed Monte Carlo simulations for protein adsorption on polymer-coated surfaces (Chapter 6, to be submitted as E.L.P. Dumont, A.V. Guillaume, A. Gore, and H. Hess, Random Sequential Adsorption of proteins on polymer-covered surfaces: A simulation-based approach) and I explored a molecular model to explain the fracture of materials at low stresses (Chapter 7).