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The primary goal of the Cell and Protein Mechanics group is to discover, measure and model the pathways by which key mechanical proteins acquired their contemporary structures. Two of our primary proteins of interest are tubulin and collagen. Tubulin is a protein that enables mitosis by assembling into hollow, 24-nanometer diameter railways called microtubules upon which motor proteins pull daughter chromosomes away from the parent cell’s center. Microtubules are also responsible for enabling fast transport within neurons, sustaining compressive loads within cells, and forming flagella in some cells. To understand how tubulin was driven to its current form, we are using molecular dynamics simulations to mechanically characterize all known tubulin sequences. The image to the right shows a single tubulin monomer being strained in uniaxial tension. What we have found is that tubulin's elastic modulus is scale dependent. This is not a phenomenon typically seen at the macroscale. However, at the nanoscale it often occurs. In the case of tubulin, it may dictate how large the molecule may become before it can no longer support the large compressive forces it is subjected to during mitosis and during axonal transport.
A single tubulin monomer being strained in uniaxial tension
A 30 micron AFM iamge of the Trichodesmium erythraeum
Collagen is nature’s most abundant protein, comprising roughly one third of the total protein mass in most large organisms. We are currently exploring a hypothesis that collagen, after being driven to its triple helical, triglycine repeat structure, in a large animal that required bones, tendons, and ligaments, or at least an extensive network of connective tissue to survive, was somehow horizontally transferred intron-free into the marine cyanobacterium Trichodesmium erythraeum. This transfer may have given this organism the ability to aggregate to ocean-spanning dimensions giving it the ability to acquire greater access to protein sources by allowing it to concentrate its neurotoxin. This work appears in the Journal of Molecular Evolution. At the cellular scale, we are interested in discovering the mechanisms by which cells balance the mechanical properties between their cytoskeletons and their membranes. Specifically, if cytoskeletal proteins such as tubulin and actin were to polymerize at rates and strengths that exceed the mechanical strengths of their host membranes, cell viability would be compromised. What we have discovered is that there does appear to be a "natural saftey factor" that exists between a cell and its membrane. For a cell membrane, which has an elastic modulus of approximately 100 MPa and an arial failure strain of approximately 3 - 4%, the force required to rupture is between 10 piconewtons to 1 nanonewton. The two most important cytoskeletal structures, actin filaments, and microtubules can only sustain axial loads of approximately 10% of these values. This work appears in the American Society of Mechanical Engineering Journal of Biomechanics.
A cell mechanics model of actin filament interacting with a cell membrane
Veeco Instrument 3100 Nanoscope with a Zyvex L100 nanomanipulator
To help answer these questions, we are developing an integrated atomic force microscopy nanomanipulation system to simultaneously image and strain small biological samples. This unique device, shown to the left, incorporates a Veeco Instruments Dimension 3100 Nanoscope with a Zyvex L100 nanomanipulator. The device, currently under patent review, is capable of simultaneous nanomanipulation and nanoscale imaging.. Typically, an AFM may operate in either imaging mode or manipulation mode independently, but not simultaneously. This device will enable the imaging of single cells and proteins as they are being deformed, yielding valuable information as to how cells and proteins sustain mechanical loads both in vivo and in vitro. As cell and protein mechanics becomes more prevalent and relevant to medicine, the need for enhanced measurement techniques also becomes more pressing. To address this issue, we have developed a method for performing small-scale mechanics experiments in parallel through the use of a highly compliant microfabricated polymeric microbeam array.
Calibrating the PDMS microbeam array with an AFM cantilever.
SEM micrograph PDMS array. This work appears in the Journal of Micromechanics and Microengineering.
The Zyvex L100 being used to measure electrical properties of a deforming nanotube.
With the help of funding from the Keck Foundation, we have begun to understand the relationship between nanomechanics and electrical transport. One of the major goals of the Keck Institute for Attofluidics at Drexel University is to develop a unique set of nanoscale probes, primarily using multi-walled carbon nanotubes to probe the nanoscale electrical, mechanical, and chemical environments of single cells. An important step towards this goal is in understanding how the electrical properties of these small structures change as they are deformed. To the left is a series of images performed inside a scanning electron microscope with the Zyvex L100 being used to both maneuver the nanotube mechanically and to measure its electrical properties as it deforms. The remarkable thing about these structures, is that unlike a traditional borosilicate glass pipette, these nanotube structures can regain their original shape even after large-scale buckling. This is a similar deformation mode that you have likely seen with a plastic drinking straw. By using these carbon-nanotube pipettes, it is our hope that we will be able to more reliably and accurately probe single cells. We are using microfabrication methods and modeling techniques to design a device for sorting red blood cells for the purpose of accelerating complete blood counting methods.
SEM images of top view (left) and side view (right) of a two-layer square-post device prior to Pyrex bonding. Scale bars = 20 mm.
SEM images of top view (left) and side view (right) of a two-layer trapezoidal-post device prior to bonding. Scale bars = 20 mm.
The Dragon Wagon
The Cell and Protein Mechanics Laboratory is also dedicated to the mission of reducing and reversing the negative impacts that humans have had on the environment. In particular, we are working on a pair of sustainable transportation systems devised to 1) slow the obesity and diabetes epidemics, 2) cut back on greenhouse gas emissions and particulate emissions, and 3) reduce current manifestations of human violence caused by unequal access to oil. These two transportation systems are the human-electric-solar taxi and the bicycle highway. Both are designed to make urban and suburban environments, cooler, quieter and less entropic by encouraging people to limit automobile use. This work has appeared in the Proceedings of the ASME, and recently in Recent Patents in Nanotechnology.
Highlights from ASME Human Powered Vehicle Competition 2008
Philadelphia Mayor Michael Nutter on DragonWagon 2.0 During National Bike to Work Week
Recent Patents in Bionanotechnologies: Nanolithography,
Bionanocomposites, Cell-Based Computing and Entropy Production.This is a paper that was recently written on several new patents in bionanotechnology. The topics cover are rather eclectic. They range from bionanocomposites, to cellular computing. A concept was introduce that I call mechanoevolution that classifies all machines as either sources or sinks of entropy, which has implications for the second law of thermodynamics as it applies to living versus non-living systems.
Quantitative model of entropy production in a universe with and without life, which strives to reduce entropy locally.
Bicycle Highway Design
Design and implementation of a dedicated bicycle highway infrastructure for reduction of obesity, greenhouse gas emissions and dependence on foreign oil.
The broader long-term vision of the Cell and Protein Mechanics Laboratory is to help create a unified framework under which humans and machines will ultimately co-evolve into a new form of life, through the process of mechanoevolution.
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