Molecular motors are nature's nanomachines, and are the essential agents of movement that are an integral part of many living organisms. These motors performance in terms of mechanical efficiency is very superior and unparalleled by any man made motors. Molecular motors do a variety of functions, for example, causing contraction of cardiac muscle for every heart beat, and causing the smooth muscle in our intestines to contract slowly as we digest our food. Myosins, kinesins and dyneins are best-known examples of the three families of naturally occurring motor molecules. Each family has members that transport vesicles through cell cytoplasm along linear assemblies of molecules. All these motor molecules function by undergoing shape changes utilizing energy from the biological fuel ATP (adenosine triphosphate). In contrast to single molecule motors, multi-protein complexes containing several molecules also exist in nature. The nuclear pore complex (NPC) is such a nanoscale supramolecular motor. The nuclear pore complex operates primarily via energy dependent processes, and performs some of the most vital functions required for the survival of a cell. A nuclear pore complex, with typical dimensions of 100-200 nm, is a megadalton (MDa) heteromultimeric protein complex, which spans the nuclear envelope and is postulated to possess a transporter-containing central cylindrical body embedded between cytoplasmic and nucleoplasmic rings [1-4]. A cell has many, presumably identical, NPCs, each of which participates in the import and export of nuclear material from within the nucleus [1,3]. In the presence of appropriate chemical stimuli, the NPC opens or closes, like a gating mechanism, and permits the flow of material in to and out of the nucleus. Exactly how this transport occurs through the NPC is an open question, and a very important one, with profound implications for nanoscale devices for fluidic transport, genetic engineering and targeted drug delivery.
Atomic force microscopy confirms that the open and closed states of the NPC correspond with normal and restricted nuclear import, respectively. High resolution imaging of the cytoplasmic surface of individual nuclear pore complexes showed the characteristic toroid-shape structure comprising a deep central pore surrounded by a ring-like distribution of peaks. In cellular hypertrophy, a pathological condition altering the entire metabolic and physical structure of the cell, the central pore appeared plugged. We believe that understanding and simulation of this bio-motor can provide us with unique solutions for designing nanoscale motors for engineering applications.
Two different analysis models were developed and investigated to find the mechanical characteristics and compared between them. As a first step in understanding the mechanical characteristics of the NPC, a preliminary study was conducted to understand the pressure-velocity characteristics. Two different analysis models consisting of NPC containing the central plug, bottom basket and top cytoplasm rings were developed, and investigated to find the mechanical characteristics and compared between them. A coupled fluid-solid analysis was performed on both the models. Preliminary results of pressure and velocities profiles obtained from the models are presented and discussed. Based on the results, the design implications will be discussed.
The authors thank Dr. Marc Gacy for helpful discussions and the AFM images of NPC's. The first author thanks the Office of Professional Development of IUPUI and the Department of Mechanical Engineering for their support.
1. C.W. Akey, M. Radmacher, J. Cell. Biol. 122, 1-19 (1993).
2. N. Pante, U. Aebi, Curr. Opin. Struct. Biol. 4, 187-196 (1996).
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