Publications

Bollinger, Jonathan B.; Stevens, Mark J.

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Bollinger, Jonathan B.; Stevens, Mark J.

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Bollinger, Jonathan B.; Stevens, Mark J.

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Bollinger, Jonathan B.; Stevens, Mark J.; Frischknecht, Amalie F.

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Physical Review Letters

Innes-Gold, Sarah N.; Pincus, Philip A.; Stevens, Mark J.; Saleh, Omar A.

The configuration of charged polymers is heavily dependent on interactions with surrounding salt ions, typically manifesting as a sensitivity to the bulk ionic strength. Here, we use single-molecule mechanical measurements to show that a charged polysaccharide, hyaluronic acid, shows a surprising regime of insensitivity to ionic strength in the presence of trivalent ions. Using simulations and theory, we propose that this is caused by the formation of a "jacket" of ions, tightly associated with the polymer, whose charge (and thus effect on configuration) is robust against changes in solution composition.

Stevens, Mark J.; Bollinger, Jon B.; Grest, Gary S.; Rubinstein, Michael R.

Abstract not provided.

Thurston, Bryce A.; Stevens, Mark J.; Paren, Benjamin P.; Winey, Karen I.; Frischknecht, Amalie F.

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Koski, Jason K.; Stevens, Mark J.; Krook, Nadia M.; Composto, Russell C.; Riggleman, Robert A.; Frischknecht, Amalie F.

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Stevens, Mark J.; Frischknecht, Amalie F.

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Innes-Gold, Sarah N.; Berezney, John B.; Pincus, Philip A.; Stevens, Mark J.; Saleh, Omar S.

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Spoerke, Erik D.; Russo, Sara R.; Jones, Brad H.; Martinez, Alina M.; mcgrath, dominic m.; Bollinger, Jonathan B.; Stevens, Mark J.; Bachand, George B.

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Soft Matter

Bollinger, Jonathan B.; Stevens, Mark J.

Microtubules are stiff biopolymers that self-assemble via the addition of GTP-tubulin (αβ-dimer bound to GTP), but hydrolysis of GTP- to GDP-tubulin within the tubules destabilizes them toward catastrophically-fast depolymerization. The molecular mechanisms and features of the individual tubulin proteins that drive such behavior are still not well-understood. Using molecular dynamics simulations of whole microtubules built from a coarse-grained model of tubulin, we demonstrate how conformational shape changes (i.e., deformations) in subunits that frustrate tubulin-tubulin binding within microtubules drive depolymerization of stiff tubules via unpeeling "ram's horns" consistent with experiments. We calculate the sensitivity of these behaviors to the length scales and strengths of binding attractions and varying degrees of binding frustration driven by subunit shape change, and demonstrate that the dynamic instability and mechanical properties of microtubules can be produced based on either balanced or imbalanced strengths of lateral and vertical binding attractions. Finally, we show how catastrophic depolymerization can be interrupted by small regions of the microtubule containing undeformed dimers, corresponding to incomplete lattice hydrolysis. The results demonstrate a mechanism by which microtubule rescue can occur.

Journal of Chemical Physics

Stevens, Mark J.

Very large molecular dynamics simulations with open ends between two solid adherends have been performed treating tensile deformation of coarse-grained, highly crosslinked polymer networks modeling epoxy systems. The open boundary and the presence of corners dramatically alter the fracture behavior. In contrast to systems with periodic boundaries, the failure strain decreases with increasing system size until a critical size is reached. This decrease greatly reduces the difference in the crack initiation strains between simulation and experiment. In the open geometry, the sides of the polymer network contract inward forming wedge shaped corners. The stress and strain are concentrated in the corners where the shear component is present and large. The nonuniformity of the strain results in accumulation of bond breaking in the corners and crack initiation there. Moreover, the corner strain is system size dependent, which results in a system size dependence of the failure strain.

Spoerke, Erik D.; Jones, Brad H.; Martinez, Alina M.; Wheeler, Jill S.; Ting, Christina T.; Henderson, Ian M.; McKenzie, Bonnie B.; Vervacke, Jeffrey V.; Stevens, Mark J.

Abstract not provided.

Journal of Chemical Physics

Stevens, Mark J.; Berezney, John P.; Saleh, Omar A.

We present simulations of the force-extension curves of strong polyelectrolytes with varying intrinsic stiffness as well as specifically treating hyaluronic acid, a polyelectrolyte of intermediate stiffness. Whereas fully flexible polyelectrolytes show a high-force regime where extension increases nearly logarithmically with force, we find that the addition of even a small amount of stiffness alters the short-range structure and removes this logarithmic elastic regime. This further confirms that the logarithmic regime is a consequence of the short-ranged "wrinkles" in the flexible chain. As the stiffness increases, the force-extension curves tend toward and reach the wormlike chain behavior. Using the screened Coulomb potential and a simple bead-spring model, the simulations are able to reproduce the hyaluronic acid experimental force-extension curves for salt concentrations ranging from 1 to 500 mM. Furthermore, the simulation data can be scaled to a universal curve like the experimental data. The scaling analysis is consistent with the interpretation that, in the low-salt limit, the hyaluronic acid chain stiffness scales with salt with an exponent of -0.7, rather than either of the two main theoretical predictions of -0.5 and -1. Furthermore, given the conditions of the simulation, we conclude that this exponent value is not due to counterion condensation effects, as had previously been suggested.

Nature Materials

Trigg, Edward B.; Gaines, Taylor W.; Maréchal, Manuel; Moed, Demi E.; Rannou, Patrice; Wagener, Kenneth B.; Stevens, Mark J.; Winey, Karen I.

Recent advances in polymer synthesis have allowed remarkable control over chain microstructure and conformation. Capitalizing on such developments, here we create well-controlled chain folding in sulfonated polyethylene, leading to highly uniform hydrated acid layers of subnanometre thickness with high proton conductivity. The linear polyethylene contains sulfonic acid groups pendant to precisely every twenty-first carbon atom that induce tight chain folds to form the hydrated layers, while the methylene segments crystallize. The proton conductivity is on par with Nafion 117, the benchmark for fuel cell membranes. We demonstrate that well-controlled hairpin chain folding can be utilized for proton conductivity within a crystalline polymer structure, and we project that this structure could be adapted for ion transport. This layered polyethylene-based structure is an innovative and versatile design paradigm for functional polymer membranes, opening doors to efficient and selective transport of other ions and small molecules on appropriate selection of functional groups.

Soft Matter

Bollinger, Jonathan B.; Stevens, Mark J.

Microtubules exhibit a dynamic instability between growth and catastrophic depolymerization. GTP-tubulin (αβ-dimer bound to GTP) self-assembles, but dephosphorylation of GTP- to GDP-tubulin within the tubule results in destabilization. While the mechanical basis for destabilization is not fully understood, one hypothesis is that dephosphorylation causes tubulin to change shape, frustrating bonds and generating stress. To test this idea, we perform molecular dynamics simulations of microtubules built from coarse-grained models of tubulin, incorporating a small compression of α-subunits associated with dephosphorylation in experiments. We find that this shape change induces depolymerization of otherwise stable systems via unpeeling "ram's horns" characteristic of microtubules. Depolymerization can be averted by caps with uncompressed α-subunits, i.e., GTP-rich end regions. Thus, the shape change is sufficient to yield microtubule behavior.

Bachand, George B.; Bachand, Marlene B.; Greene, Adrienne C.; Stevens, Mark J.

Abstract not provided.

Spoerke, Erik D.; Jones, Brad H.; Martinez, Alina M.; mcgrath, dominic m.; Bollinger, Jonathan B.; Stevens, Mark J.; Bachand, George B.

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Stevens, Mark J.

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Sasaki, Darryl Y.; Bachand, George B.; Spoerke, Erik D.; Stevens, Mark J.; Vandelinder, Virginia A.; Martinez, Haneen M.; Bachand, Marlene B.; Greene, Adrienne C.; Nabar, Namita N.; Paxton, Walter F.

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Spoerke, Erik D.; Bachand, George B.; Sasaki, Darryl Y.; Stevens, Mark J.; Bollinger, Jonathan B.; Jones, Brad H.; Wheeler, Jill S.; Vervacke, Jeffrey V.; Martinez, Alina M.; mcgrath, dominic m.

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Stevens, Mark J.

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Stevens, Mark J.

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Rempe, Susan R.; Stevens, Mark J.; Rogers, David M.; Vanegas, Juan M.

Enzymes that degrade specific small molecules could save lives by neutralizing threats from chemical agents in the blood or environment, or by starving pathogenic cells, but promiscuous interactions with other molecules typically limit their effectiveness by blocking the enzyme active site. An obvious solution would be to re-engineer the enzyme to enhance catalytic fidelity, but lack of understanding about how enzymes discriminate between molecules remains a formidable challenge to this approach. Our recent work in collaboration with the University of Texas (UT) suggested a new approach and a model system for understanding enzyme specificity. Asparaginase enzymes catalyze degradation of asparagine, which forms the basis of a medical treatment. Com- petition by the abundant and chemically similar molecule, glutamine, interferes with asparagine decomposition, thus hindering enzyme efficacy. Asparaginase is advantageous as a model degra- dation enzyme because variants that demonstrate different binding affinities and catalytic rates can be compared. Here, we leveraged Sandia and the University of Maryland's strengths in molecu- lar simulation, and UT experimental expertise in asparaginase modification and functional assays, to understand asparaginase specificity. Our results advanced a new hypothesis about asparagi- nase catalytic mechanism that explains for the first time why proximity between the substrate's alpha-carboxyl and carboxamide is absolutely required for catalysis. Based on those insights, we developed the first mutant (Q59L) asparaginase from E. coli that lacks activity toward glutamine. We used that mutant to show that glutaminase activity is required to kill cancer cells that have asparagine synthetase enzymes (ASNS), but not ASNS-negative cancer cells.