Polymersome delivery of siRNA and antisense oligonucleotides (2009)
Kim, Younghoon, Tewari, Manorama, Pajerowski, J. David, Cai, Shenshen, Sen, Shamik, Williams, Jason, ...
siRNA and antisense oligonucleotides, AON, have similar size and negative charge and are often packaged for in vitro delivery with cationic lipids or polymers—but exposed positive charge is...
Unfolding a Linker between Helical Repeats (2008)
Vanessa Ortiz, Steven O. Nielsen, Michael L. Klein, Dennis E. Discher
Multi-domain proteins prove to be a dominant fraction of the proteome, 1 but the physical roles of linkers between domains as domain separators and/or connectors are not always clear. Multirepeat
Dissipative particle dynamics simulations of polymersomes (2008)
Vanessa Ortiz, Steven O. Nielsen, Dennis E. Discher, Michael L. Klein, Reinhard Lipowsky, Julian Shillcock
Brown, Andre E. X., Hategan, Alina, Safer, Daniel, Goldman, Yale E., Discher, Dennis E.
Myosin-II's rod-like tail drives filament assembly with a head arrangement that should generate equal and opposite contractile forces on actin--if one assumes that the filament is a symmetric bipole....
Dennis E. Discher, Ricky Winardi, P. Olivier Schischmanoff, Marilyn Parra, John G. Conboy
Abstract. Mechanical strength Of the red cell mem-brane is dependent on ternary interactions among the skeletal proteins, spectrin, actin, and protein 4.1. Pro-tein 4.1's spectrin-actin-binding...
Tsai, Richard K, Discher, Dennis E
Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with "self" cells that display CD47--although signaling mechanisms in self-recognition have...
Physical plasticity of the nucleus in stem cell differentiation (2007)
Pajerowski, J. David, Dahl, Kris Noel, Zhong, Franklin L, Sammak, Paul J, Discher, Dennis E
Cell differentiation in embryogenesis involves extensive changes in gene expression structural reorganization within the nucleus, including chromatin condensation and nucleoprotein immobilization. We...
Frey, Margo Tilley, Engler, Adam, Discher, Dennis E., Lee, Juliet, Wang, Yu-Li
In conjunction with surface chemistry, the mechanical properties of cell culture substrates provide important biological cues that affect cell behavior including growth, differentiation, spreading,...
Cai, Shenshen, Vijayan, Kandaswamy, Cheng, Debbie, Lima, Eliana M, Discher, Dennis E
Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly (ε-caprolactone) (PEO [5 kDa]-PCL [6.5 kDa]) in order to compare...
Shape effects of filaments versus spherical particles in flow and drug delivery (2007)
Geng, Yan, Dalhaimer, Paul, Cai, Shenshen, Tsai, Richard, Tewari, Manorama, Minko, Tamara, ...
Interaction of spherical particles with cells and within animals has been studied extensively, but the effects of shape have received little attention. Here we use highly stable, polymer micelle...
Kim, Younghoon, Tewari, Manu, Pajerowski, J. David, Sen, Shamik, Jason, Williams, Sirsi, Shashank, ...
Delivery of antisense oligonucleotides, AON, presents many of the same challenges as delivery of any nucleic acid: charge, stability, cell uptake, endolysosomal escape, and entry into the nucleus....
Discher, Dennis E, Ahmed, Fariyal
Polymersomes are self-assembled polymer shells composed of block copolymer amphiphiles. These synthetic amphiphiles have amphiphilicity similar to lipids, but they have much larger molecular weights,...
Vanessa Ortiz, Steven O. Nielsen, Michael L. Klein, Dennis E. Discher, Vanessa Ortiz, Steven O. Nielsen, ...
ABSTRACT: Atomistic, coarsegrain, and mesoscopic computer simulation methods applied recently to the study of block copolymer assemblies in solution are reviewed. At the atomic level, particle-based...
Sen, Shamik, Subramanian, Shyamsundar, Discher, Dennis E
In probing adhesion and cell mechanics by atomic force microscopy (AFM), the mechanical properties of the membrane have an important if neglected role. Here we theoretically model the contact of an...
Power-Law Rheology of Isolated Nuclei with Deformation Mapping of Nuclear Substructures (2005)
Dahl, Kris, Engler, Adam J, Pajerowski, J. David, Discher, Dennis E
Force-induced changes in genome expression as well as remodeling of nuclear architecture in development and disease motivate a deeper understanding of nuclear mechanics. Chromatin and green...
Parthasarathy, Ranganath, Subramanian, Shyamsundar, Boder, Eric T, Discher, Dennis E.
Display of heterologous proteins on the surface of Saccharomyces cerevisiae is increasingly being exploited for directed evolution because of straightforward cell screens. However, yeast...
Shamik Sen, Shyamsundar Subramanian, Dennis E. Discher
ABSTRACT In probing adhesion and cell mechanics by atomic force microscopy (AFM), the mechanical properties of the membrane have an important if neglected role. Here we theoretically model the...
Adhesion-contractile balance in myocyte differentiation (2004)
Griffin, Maureen A., Sen, Shamik, Sweeney, H. Lee, Discher, Dennis E
Tissue cells generally pull on their matrix attachments and balance a quasi-static contractility against adequate adhesion, but any correlation with and/or influence on phenotype are not yet...
Topographical Pattern Dynamics in Passive Adhesion of Cell Membranes (2004)
Hategan, Alina, Sengupta, Kheya, Kahn, Samuel, Sackmann, Erich, Discher, Dennis E
Strong adhesion of highly active cells often nucleates focal adhesions, synapses, and related structures. Red cells lack such complex adhesion systems and are also nonmotile, but they are shown here...
Engler, Adam J, Richert, Ludovic, Wong, Joyce, Picart, Catherine, Discher, Dennis E
Surface probe measurements of the elasticity of thin-film matrices as well as biological samples prove generally important to understanding cell attachment across such systems. To illustrate this,...
Engler, Adam J., Griffin, Maureen A., Sen, Shamik, Bönnemann, Carsten G., Sweeney, H. Lee, Discher, Dennis E
Contractile myocytes provide a test of the hypothesis that cells sense their mechanical as well as molecular microenvironment, altering expression, organization, and/or morphology accordingly. Here,...
Elongation and Fluctuations of Semi-flexible Polymers in a Nematic Solvent (2004)
Dogic, Z., Zhang, J., Lau, A. W.C., Aranda-Espinoza, Helim, Dalhaimer, Paul M, Discher, Dennis E, ...
We directly visualize single polymers with persistence lengths ranging from lp = 0:05 to 16 µm, dissolved in the nematic phase of rod-like fd virus. Polymers with sufficiently large persistence...
Patterning, Prestress, and Peeling Dynamics of Myocytes (2004)
Griffin, Maureen A., Engler, Adam J., Barber, Thomas A., Healy, Kevin E., Sweeney, H. Lee, Discher, Dennis E
As typical anchorage-dependent cells myocytes must balance contractility against adequate adhesion. Skeletal myotubes grown as isolated strips from myoblasts on micropatterned glass exhibited...
Substrate Compliance versus Ligand Density in Cell on Gel Responses (2004)
Engler, Adam, Bacakova, Lucie, Newman, Cynthia, Hategan, Alina, Griffin, Maureen, Discher, Dennis E
Substrate stiffness is emerging as an important physical factor in the response of many cell types. In agreement with findings on other anchorage-dependent cell lineages, aortic smooth muscle cells...
Kris Noel Dahl, Samuel M. Kahn, Katherine L. Wilson, Dennis E. Discher
The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber
Pore Stability and Dynamics in Polymer Membranes (2003)
Bermudez, Harry, Aranda-Espinoza, Helim, Hammer, Daniel A, Discher, Dennis E
Vesicles self-assembled from amphiphilic diblock copolymers exhibit a wide diversity of behavior upon poration, due to competitions between edge, surface and bending energies, while viscous...
Law, Richard, Liao, George, Harper, Sandy, Yang, Guoliang, Speicher, David W., Discher, Dennis E
Pathways of unfolding a protein depend in principle on the perturbation--whether it is temperature, denaturant, or even forced extension. Widely-shared, helical-bundle spectrin repeats are known to...
Adhesively-Tensed Cell Membranes: Lysis Kinetics and Atomic Force Microscopy Probing (2003)
Hategan, Alina, Law, Richard, Kahn, Samuel, Discher, Dennis E
Membrane tension underlies a range of cell physiological processes. Strong adhesion of the simple red cell is used as a simple model of a spread cell with a finite membrane tension--a state which...
Networks with fourfold connectivity in two dimensions (2003)
Tessier, Frédéric, Boal, David H., Discher, Dennis E
The elastic properties of planar, C4-symmetric networks under stress and at nonzero temperature are determined by simulation and mean field approximations. Attached at fourfold coordinated junction...
Cooperativity in Forced Unfolding of Tandem Spectrin Repeats (2003)
Law, Richard, Carl, Philippe, Harper, Sandy, Dalhaimer, Paul M, Speicher, David W, Discher, Dennis E
Force-driven conformational changes provide a broad basis for protein extensibility, and multidomain proteins broaden the possibilities further by allowing for a multiplicity of forcibly extended...
Simulation of Diblock Copolymer Self-Assembly, Using a Coarse-Grain Model (2003)
Goundla Srinivas, John C. Shelley, Steve O. Nielsen, Dennis E. Discher, Michael L. Klein
A coarse-grain model for amphiphilic diblock copolymers is developed by fitting the required parameters to properties taken from all-atom molecular dynamics simulations and experimental data....
Pore Stability and Dynamics in Polymer Membranes (2002)
Bermudez, Harry, Aranda-Espinoza, Helim, Hammer, Daniel A., Discher, Dennis E.
Vesicles self-assembled from amphiphilic diblock copolymers exhibit a wide diversity of behavior upon electroporation, due to competitions between edge, surface and bending energies that drive the...
Domain unfolding in neurofilament sidearms: effects of phosphorylation and ATP (2002)
Aranda-Espinoza, Helim, Carl, Philippe, Leterrier, Jean-François, Janmey, Paul, Discher, Dennis E
Lateral projections of neuro¢laments (NF) called sidearms (SA) a¡ect axon stability and caliber. SA phosphorylation is thought to modulate inter-NF distance and interactions between NF and...
Lee, James C-M., Discher, Dennis E
To assess local elasticity in the red cell's spectrin-actin network, nano-particles were tethered to actin nodes and their constrained thermal motions were tracked. Cells were both immobilized and...
Electromechanical Limits of Polymersomes (2001)
Aranda-Espinoza, Helim, Bermudez, Harry, Bates, Frank S, Discher, Dennis E
Self-assembled membranes of amphiphilic diblock copolymers enable comparisons of cohesiveness with lipid membranes over the range of hydrophobic thicknesses d = 3-15 nm. At zero mechanical tension...
Molecular Weight Dependence of Polymersome Membrane Elasticity and Stability (2001)
Bermudez, Harry, Brannan, Aaron K., Hammer, Daniel A., Bates, Frank S., Discher, Dennis E.
Vesicles prepared in water from a series of diblock copolymers and termed "polymersomes" are physically characterized. With increasing molecular weight $\bar{M}_n$, the hydrophobic core thickness $d$...
Actin Protofilament Orientation in Deformation of the Erythrocyte Membrane Skeleton (2000)
Picart, Catherine, Dalhaimer, Paul M, Discher, Dennis E
The red cell's spectrin-actin network is known to sustain local states of shear, dilation, and condensation, and yet the short actin filaments are found to maintain membrane-tangent and near-random...
Simulations of the erythrocyte cytoskeleton at large deformation. ii. micropipette aspiration (1998)
Dennis E. Discher, David H. Boal, Seng K. Boey
ABSTRACT Coarse-grained molecular models of the erythrocyte membrane’s spectrin cytoskeleton are presented in Monte Carlo simulations of whole cells in micropipette aspiration. The nonlinear chain...
Forced unfolding modulated by disulfide bonds in the Ig domains of a cell adhesion molecule
Carl, Philippe, Kwok, Carol H., Manderson, Gavin, Speicher, David W., Discher, Dennis E.
Cell adhesion molecules (CAMs) mediate cell attachment and stress transfer through extracellular domains. Here we forcibly unfold the Ig domains of a prototypical Ig superfamily CAM that contains...
Cooperativity in Forced Unfolding of Tandem Spectrin Repeats
Law, Richard, Carl, Philippe, Harper, Sandy, Dalhaimer, Paul, Speicher, David W., Discher, Dennis E.
Force-driven conformational changes provide a broad basis for protein extensibility, and multidomain proteins broaden the possibilities further by allowing for a multiplicity of forcibly extended...
Adhesively-Tensed Cell Membranes: Lysis Kinetics and Atomic Force Microscopy Probing
Hategan, Alina, Law, Richard, Kahn, Samuel, Discher, Dennis E.
Membrane tension underlies a range of cell physiological processes. Strong adhesion of the simple red cell is used as a simple model of a spread cell with a finite membrane tension—a state which...
Pathway Shifts and Thermal Softening in Temperature-Coupled Forced Unfolding of Spectrin Domains
Law, Richard, Liao, George, Harper, Sandy, Yang, Guoliang, Speicher, David W., Discher, Dennis E.
Pathways of unfolding a protein depend in principle on the perturbation—whether it is temperature, denaturant, or even forced extension. Widely-shared, helical-bundle spectrin repeats are known to...
Patterning, Prestress, and Peeling Dynamics of Myocytes
Griffin, Maureen A., Engler, Adam J., Barber, Thomas A., Healy, Kevin E., Sweeney, H. Lee, Discher, Dennis E.
As typical anchorage-dependent cells myocytes must balance contractility against adequate adhesion. Skeletal myotubes grown as isolated strips from myoblasts on micropatterned glass exhibited...
Topographical Pattern Dynamics in Passive Adhesion of Cell Membranes
Hategan, Alina, Sengupta, Kheya, Kahn, Samuel, Sackmann, Erich, Discher, Dennis E.
Strong adhesion of highly active cells often nucleates focal adhesions, synapses, and related structures. Red cells lack such complex adhesion systems and are also nonmotile, but they are shown here...
Power-Law Rheology of Isolated Nuclei with Deformation Mapping of Nuclear Substructures
Dahl, Kris Noel, Engler, Adam J., Pajerowski, J. David, Discher, Dennis E.
Force-induced changes in genome expression as well as remodeling of nuclear architecture in development and disease motivate a deeper understanding of nuclear mechanics. Chromatin and green...
Indentation and Adhesive Probing of a Cell Membrane with AFM: Theoretical Model and Experiments
Sen, Shamik, Subramanian, Shyamsundar, Discher, Dennis E.
In probing adhesion and cell mechanics by atomic force microscopy (AFM), the mechanical properties of the membrane have an important if neglected role. Here we theoretically model the contact of an...
Forced unfolding modulated by disulfide bonds in the Ig domains of a cell adhesion molecule
Carl, Philippe, Kwok, Carol H., Manderson, Gavin, Speicher, David W., Discher, Dennis E.
Cell adhesion molecules (CAMs) mediate cell attachment and stress transfer through extracellular domains. Here we forcibly unfold the Ig domains of a prototypical Ig superfamily CAM that contains...
Cooperativity in Forced Unfolding of Tandem Spectrin Repeats
Law, Richard, Carl, Philippe, Harper, Sandy, Dalhaimer, Paul, Speicher, David W., Discher, Dennis E.
Force-driven conformational changes provide a broad basis for protein extensibility, and multidomain proteins broaden the possibilities further by allowing for a multiplicity of forcibly extended...
Adhesively-Tensed Cell Membranes: Lysis Kinetics and Atomic Force Microscopy Probing
Hategan, Alina, Law, Richard, Kahn, Samuel, Discher, Dennis E.
Membrane tension underlies a range of cell physiological processes. Strong adhesion of the simple red cell is used as a simple model of a spread cell with a finite membrane tension—a state which...
Pathway Shifts and Thermal Softening in Temperature-Coupled Forced Unfolding of Spectrin Domains
Law, Richard, Liao, George, Harper, Sandy, Yang, Guoliang, Speicher, David W., Discher, Dennis E.
Pathways of unfolding a protein depend in principle on the perturbation—whether it is temperature, denaturant, or even forced extension. Widely-shared, helical-bundle spectrin repeats are known to...
Patterning, Prestress, and Peeling Dynamics of Myocytes
Griffin, Maureen A., Engler, Adam J., Barber, Thomas A., Healy, Kevin E., Sweeney, H. Lee, Discher, Dennis E.
As typical anchorage-dependent cells myocytes must balance contractility against adequate adhesion. Skeletal myotubes grown as isolated strips from myoblasts on micropatterned glass exhibited...
Topographical Pattern Dynamics in Passive Adhesion of Cell Membranes
Hategan, Alina, Sengupta, Kheya, Kahn, Samuel, Sackmann, Erich, Discher, Dennis E.
Strong adhesion of highly active cells often nucleates focal adhesions, synapses, and related structures. Red cells lack such complex adhesion systems and are also nonmotile, but they are shown here...
Power-Law Rheology of Isolated Nuclei with Deformation Mapping of Nuclear Substructures
Dahl, Kris Noel, Engler, Adam J., Pajerowski, J. David, Discher, Dennis E.
Force-induced changes in genome expression as well as remodeling of nuclear architecture in development and disease motivate a deeper understanding of nuclear mechanics. Chromatin and green...
Indentation and Adhesive Probing of a Cell Membrane with AFM: Theoretical Model and Experiments
Sen, Shamik, Subramanian, Shyamsundar, Discher, Dennis E.
In probing adhesion and cell mechanics by atomic force microscopy (AFM), the mechanical properties of the membrane have an important if neglected role. Here we theoretically model the contact of an...
Species- and cell type-specific interactions between CD47 and human SIRPα
Subramanian, Shyamsundar, Parthasarathy, Ranganath, Sen, Shamik, Boder, Eric T., Discher, Dennis E.
CD47 on red blood cells (RBCs) reportedly signals “self” by binding SIRPα on phagocytes, at least in mice. Such interactions across and within species, from mouse to human, are not yet clear and...
Forced Unfolding of Coiled-Coils in Fibrinogen by Single-Molecule AFM
Brown, André E. X., Litvinov, Rustem I., Discher, Dennis E., Weisel, John W.
Fibrinogen is a blood plasma protein that, after activation by thrombin, assembles into fibrin fibers that form the elastic network of blood clots. We used atomic force microscopy to study the forced...
Engler, Adam J., Griffin, Maureen A., Sen, Shamik, Bönnemann, Carsten G., Sweeney, H. Lee, Discher, Dennis E.
Contractile myocytes provide a test of the hypothesis that cells sense their mechanical as well as molecular microenvironment, altering expression, organization, and/or morphology accordingly. Here,...
Physical plasticity of the nucleus in stem cell differentiation
Pajerowski, J. David, Dahl, Kris Noel, Zhong, Franklin L., Sammak, Paul J., Discher, Dennis E.
Cell differentiation in embryogenesis involves extensive changes in gene expression structural reorganization within the nucleus, including chromatin condensation and nucleoprotein immobilization. We...
Johnson, Colin P., Gaetani, Massimiliano, Ortiz, Vanessa, Bhasin, Nishant, Harper, Sandy, Gallagher, Patrick G., ...
Pathogenic mutations in α and β spectrin result in a variety of syndromes, including hereditary elliptocytosis (HE), hereditary pyropoikilocytosis (HPP), and hereditary spherocytosis (HS). Although...
Tsai, Richard K., Discher, Dennis E.
Phagocytosis of foreign cells or particles by macrophages is a rapid process that is inefficient when faced with “self” cells that display CD47—although signaling mechanisms in self-recognition...