Dennis E. Discher Ph.D.
Professor

School of Engineering and Applied Science

Depts. of Chemical & Biomolecular,
Mechanical, and Bio- Engineering   and
Graduate Groups in Physics  &   Cell and Molecular Biology

Institute for Medicine and Engineering

Pennsylvania Muscle Institute

NSF-MRSEC Laboratory for Research on Structure of Matter/ Soft Materials group Co-Leader

NSF-NSEC NanoScience & Eng'g. Center

Wistar Institute - Structural Biology Program (Adjunct)
PUBLISHED RESEARCHLINKS:
Cell Biophysics, Biochemistry, & Biology...

Nanocarriers...
Single Molecule Biophysics...
Polymeric Self-Assemblies...

Education

• Post-doctoral Fellow (1995-1996) N.S.F. International Fellow in Physics/Biophysics, CanadianInstitute of Advanced Research, Univ. of British Columbia, Simon Fraser University,BC, Canada
• Ph.D. (1993) University of California,Berkeley  and University of California, San Francisco
• B.S. (1986) with Highest Honors, University of California, Davis

Recent Honors, Awards, Editorial Boards

• Best Paper Award 2004 - Journal of Controlled Release 
• F.W. Bessel Award from the Humboldt Fdn. of Germany
• Heilmeier Research Award
• Science Editorial Board Member
• NSF Presidential Early Career Award for Scientists and Engineers

Research Support

• NSF PECASE and NSF NanoBio Program (PI) 
• NIH R01’s and R21’s (NHLBI, NIBIB) (PI)
• Whitaker Foundation (PI) 
• MDA (Muscular Dystrophy Association)(PI) 
• NIH-BRP (coPI) 
• NSF MRSEC (co-Inv)
• NSF NSEC (co-Inv)
• Penn-Drexel NanoTech Inst. (co-Inv)
• Penn-Tobacco Settlement Fund (PI)
• NASA (coPI)
• AHA Pre-doc Fellowships (PI)
• Whitaker Fdn Pre-doc Fellowships (PI)

We focus on membrane and interface aspects of cells, relevant biomolecules, and self-assembling polymers for novel material and drug delivery nano-systems. We use and develop single molecule and single cell manipulation methods, microscopies, molecular and cell biological systems & expression, computational statistical mechanics approaches, and appropriate field theories. The research is highly interdisciplinary and draws from expertise in the biologicalsciences, physics, chemistry, and engineering.
CLICK ON:
Cell Biophysics, Biochemistry, & Biology...

Nanocarriers...
Single Molecule Biophysics...
Polymeric Self-Assemblies...

Peer-Reviewed Publications
(selected from over 100 papers)

Materials Biology & Delivery

• A. Engler, S. Sen, H.L. Sweeney, D.E. Discher*. Matrix elasticity directs stem cell lineage specification. Cell 126: 677-689 (2006).
• D.E. Discher*, P. Janmey, Y-L. Wang. Tissue cells feel and respond to the stiffness of their substrate. Science 310: 1139-1143 (2005).
• D.E. Discher*, F. Ahmed. Polymersomes. Ann Rev Bio. Eng. 8: 323-341 (2006).
• F. Ahmed, R. Pakunlu, G. Srinivas, A. Brannon, F.S. Bates, M.L. Klein, T. Minko, and D.E. Discher. Shrinkage of a rapidly growing tumor by drug-loaded Polymersomes: pH-Triggered release through copolymer degradation. ACS – Molecular Pharmaceutics 3: 340-350 (2006).
• Y. Geng and D.E. Discher. Hydrolytic shortening of polycaprolactone-block-(polyethylene oxide) worm micelles. Journal of the American Chemical Society 127: 12780-12781 (2005).
• Y. Kim, P. Dalhaimer, D. Christian, and D.E. Discher. Polymeric worm micelles as nano-carriers for drug delivery. Nanotechnology 16: S484-S491 (2005).
• P. Dalhaimer, A. Engler, R. Parthasarthy, and D.E. Discher. Targeted worm micelles. Biomacromolecules 5: 1714-1719 (2004).
• F. Ahmed and D.E. Discher. Controlled release from polymersome vesicles blended with PEO-PLA or related hydrolysable copolymer. Journal of Controlled Release 96: 37-53 (2004). ** Best Paper Award 2004: Jorge Heller Award **
• A. Engler, L. Bacakova, C. Newman, A.Popescu, M. Sheehan, and D.E. Discher. Substrate compliance versus ligand density in cell on gel responses. Biophysical Journal 86: 617-628 (2004).
• Engler, L Richert, J. Wong, C. Picart, and D.E. Discher. Surface probe measurements of the elasticity of sectioned tissue and thin gels: correlations between substrate stiffness and cell adhesion. Surface Science 570: 142-154 (2004).
• P. Photos, B.M. Discher,L. Bacakova, F.S. Bates, and D.E. Discher .  Polymersomes in vivo: increased stealth with both PEG density and molecularweight. Journal of Controlled Release 90: 323-334 (2003).
• D.E. Discher * and Adi Eisenberg.  Polymer Vesicles. Science 297: 967-973 (2002). (*corresponding author of invited review).
• J.C-M. Lee, H. Bermudez, B.M. Discher, M.A. Sheehan, Y.-Y. Won, F.S. Bates, and D.E. Discher . Preparation, stability, and in vitro performance of vesicles made with diblockcopolymers. Biotechnology and Bioengineering 73:135-145 (2001).
• D.E. Discher, P. Photos, F. Ahmed, R. Parthasarathy, and F.S. Bates. Polymersomes: A New Platform for Drug Targeting. (invited chapter) in Biomedical Aspects of Drug Targeting, editors: V.R. Muzykantov and V.P. Torchilin. Kluwer Academic Press (2002).

Single Molecule Biophysics

• N. Bhasin, R. Law, G. Liao, D. Safer, J. Elmer, B.M. Discher, H.L. Sweeney, and D.E. Discher. Molecular extensibility of mini-dystrophins and a dystrophin rod construct. Journal of Molecular Biology 352: 795-806 (2005).
• V. Ortiz, S. Nielsen, M.L. Klein, and D.E. Discher. Unfolding a linker between helical repeats. Journal of Molecular Biology 349: 638-647 (2005).
• R. Law, N. Bhasin, and D.E. Discher. Application of Probe Microscopy to Protein Unfolding: Adsorption and Ensemble Analyses. (invited chapter) in ACS Books: Applications of Scanned Probe Microscopy to Polymers, editors: J.D. Batteas, C.A. Michaels, and G.C. Walker. ACS Books. (2005)
• N. Bhasin, P. Carl, S. Harper, G. Feng, H. Lu, D.W. Speicher, and D.E. Discher. Chemistry on a single protein, VCAM-1, during forced unfolding. Journal of Biological Chemistry 279: 45865-45874 (2004).
• R. Law, S. Harper, D.W.Speicher, and D.E. Discher.  Influence of lateral association on forced unfolding of antiparallel spectrin heterodimers. Journal of Biological Chemistry 279: 45865-45874  (2004).
• R. Law, G. Liao, S. Harper,G. Yang, D.W. Speicher, and D.E. Discher.  Pathway shifts and thermal softening in temperature-coupled forced unfoldingof spectrin domains. Biophysical Journal 85:3286-3293 (2003).
• R. Law, P. Carl, S. Harper, P. Dalhaimer, D.W. Speicher, and D.E. Discher.  Cooperativity in forced unfolding of tandem spectrin repeats. Biophysical Journal 84: 533-544 (2003).
• H. Aranda-Espinoza, P.Carl, J-F. Letterier, P.A. Janmey, and D.E. Discher.  Domain Unfoldingin Neurofilament Sidearms: Effects of Phosphorylation and ATP. FEBS Letters 531: 397-401 (2002).
• P. Carl, C. Kwok, G. Manderson, D.W. Speicher, and D.E. Discher.  Forced unfolding modulated by disulfide bonds in the immunoglobulin domains of a cell adhesionmolecule. Proceedings of the National Academy of Sciences - USA 98:1565-1570 (2001).

Nano-Systems, Polymer Vesicles, & Soft Matter

• K. Vijayan, Y. Geng, and D.E. Discher. Electric field manipulation of charged copolymer worm micelles. Journal of Physical Chemistry B 110: 3831-3834 (2006).
• G. Srinivas, D.E. Discher, and M.L. Klein. Key roles for chain flexibility in block copolymer membranes that contain pores or make tubes. NanoLetters 5: 2343-2349 (2005).
• Y. Geng, F. Ahmed, N. Bhasin, and D.E. Discher. Visualizing worm micelle dynamics and phase transitions of a charged diblock copolymer in water. Journal of Physical Chemistry B 109: 3772-3779 (2005).
• G. Srinivas, D.E. Discher, and M.L. Klein. Self assembly and properties of diblock copolymers via coarse grain molecular dynamics. Nature Materials 3: 638-644 (2004). With accompanying News and Views by R. Lipowsky.
• P. Dalhaimer, H. Bermudez,and D.E. Discher. Biopolymer mimickry with polymericworm micelles: MW-scaled flexibility, locked-in curvature, and coexistingmicrophases. Journal of Polymer Science –Polymer Physics  B42:  168-172 (2004).

• H. Bermudez, H. Aranda-Espinoza,D.A. Hammer, and D.E. Discher. Pore stability and dynamics in polymer membranes. Europhysics Letters 64:4-10 (2003).

• D.E. Discher. Biomimetic Nanostructures (from Self-Assembly). (invited chapter) in Nanoscale Science and Engineering, editors: Di Ventra, S. Evoy, Heflin. Kluwer Academic Press. (2004).

• P. Dalhaimer, F.S. Bates,and D.E. Discher. Single molecule visualizationof stiffness-tunable, flow conforming worm micelles. Macromolecules 36: 6873-6877(2003).

• J.C-M. Lee, M. Santore,F.S. Bates, and D.E. Discher.   From membranes to melts, Rouse to reptation:  diffusion in polymersome versuslipid bilayers. Macromolecules, 35: 323-326 (2002).

• B.M. Discher', H. Bermudez' , Y.-Y. Won, D.A. Hammer, F.S. Bates, and D.E. Discher*.  Crosslinkedcopolymer vesicles with broadly tunable stability. Journal of Physical Chemistry  B106: 2848-2854 (2002). ('co-authors) (*correspondingauthor).

• J.C-M. Lee, R. Law,and D.E. Discher.  Bending contributions to the hydration of phospholipid and block copolymer membranes - Correlations betweenprobe fluorescence and the thermoelastic properties of vesicles. Langmuir 17:3592-3597 (2001).

• H. Aranda-Espinoza, H. Bermudez, F.S. Bates, and D.E. Discher.  Electromechanical limits of polymersomes. Physical Review Letters 87: 208301 / 1-4 (2001).

• B.M. Discher, Y.-Y. Won, D.S. Ege, J.C-M. Lee, F.S. Bates, D.E. Discher ,* and D.A. Hammer*. (*corresponding authors)  Polymersomes: tough vesicles made from diblock copolymers. Science 284:1143-1146 (1999).

• D.E. Discher, D.H. Boal,and S.K. Boey. Phase transitions and anisotropic responses of planar triangularnets under large deformation. Physical  Review E 55:4762-4772(1997)

Cell Biophysics, Biochemistry, and Biology

• Adam Engler, Shamik Sen, H.Lee Sweeney, D.E. Discher*. Matrix elasticity directs stem cell lineage specification. Cell 126: 677-689 (2006).
• S. Subramanian, R. Parthasarthy, E. Boder, and D.E. Discher. Species- and cell-specific adhesive interactions between CD47 and human SIRPa. Blood 107: 2548-2556 (2006).
• S. Sen, S. Subramanian, and D.E. Discher. Indentation and adhesive probing of a cell membrane with AFM: model and experiments. Biophysical Journal (on-line 2005).
• K.N. Dahl, A. Engler, J.D. Pajerowski, and D.E. Discher. Power law rheology of isolated nuclei with deformation mapping of nuclear sub-structures Biophysical Journal (on-line 2005).
• M. Griffin, H. Feng, M. Tewari, P. Acosta, M. Kawana, H.L. Sweeney, and D.E. Discher. g-Sarcoglycan deficiency increases cell contractility, apoptosis, and MAPK pathway activation but does not affect adhesion. Journal of Cell Science 118: 1405-1416 (2005). ** Cover Article and accompanying Editor's Highlight. **
• K.N. Dahl, S.M. Kahn, K.L. Wilson, and D.E. Discher. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. Journal of Cell Science 117: 4779-4786 (2004). ** With accompanying Editor's Highlight. And Highlight in Nature **
• M. Griffin, S. Sen, H.L. Sweeney, and D.E. Discher. Adhesion-contractile balance in myocyte differentiation. Journal of Cell Science 117: 5855-5863 (2004). ** With accompanying Editor's Highlight. **
• A. Engler, L. Bacakova, C. Newman, A. Hategan, M. Griffin, and D.E. Discher. Substrate compliance versus ligand density in cell on gel responses. Biophysical Journal 86: 617-628 (2004).
• A. Engler, M. Sheehan, S. Sen, C. Bonnemann, H.L. Sweeney, and D.E. Discher. Myotubes Differentiate Optimally on Substrates with Tissue-like Stiffness: Pathological Implications of Stiff or Soft Microenvironments. Journal of Cell Biology 166(6): 877-887 (2004). ** With accompanying Editor's Highlight. And Highlight in Nature **
• M. Sheehan, A. Engler,T. Barber, K.E. Healy, H.L. Sweeney, and D.E. Discher.  Patterning, Prestress, and Peeling dynamics of myocytes. Biophysical Journal 86: 1209-1222 (2004).

• A. Popescu, R. Law, S.Kahn, and D.E. Discher.  Adhesively tensed erythrocyte membrane: lysis dynamics and AFM probing. Biophysical Journal 85: 2746-2759(2003).

• K.N. Dahl, R. Parthasarthy,C. Westhoff, and D.E. Discher.  The role of human protein 4.2 in the attachment of CD47 to the red cell cytoskeleton. Blood 103: 1131-1136 (2004).

• K.N. Dahl, C. Westhoff,and D.E. Discher.  Fractional attachmentof CD47 (IAP) to the erythrocyte cytoskeleton and visual co-localizationwith Rh protein complexes. Blood 101: 1194-1199 (2003).

• J.C-M. Lee and D.E.Discher .  Deformation-enhanced fluctuations in the red cell skeletonwith theoretical relations to elasticity, connectivity, and spectrin unfolding. Biophysical Journal 81: 3178-3192 (2001).

• D.E. Discher. New insights into red cell membrane organization and micro-elasticity. (invitedreview) Current Opinion in Hematology 7: 117-122 (2000).

• H. Ra, C. Picart, H.Feng, H.L. Sweeney, and D.E. Discher.  Muscle cell peeling from micropatterned collagen: direct probing of focal and molecular properties of adhesion. Journal of Cell Science 12: 1425-1435 (1999).

• D.E. Discher, D.H. Boal,and S.K. Boey. Simulations of the erythrocyte cytoskeleton at large deformationII:  micropipette aspiration. Biophysical Journal 75: 1584-1597(1998).

• D.E. Discher and N. Mohandas. Kinematics of red cell aspiration by fluorescence imaged microdeformation. Biophysical Journal 71: 1680-1694 (1996).

• D.E. Discher, R. Winardi, P.O. Schischmanoff, M. Parra, J.G. Conboy, and N. Mohandas. Mechanochemistryof Protein 4.1's Spectrin-Actin Binding Domain: Ternary Complex Interactions,Membrane Binding, Network Integration, Structural Strengthening. Journalof Cell Biology 130:897-907 (1995).

• D.E. Discher, N. Mohandas, E.A. Evans. Molecular Maps of Red Cell Deformation: Hidden Elasticity andin situ Connectivity. Science 266:1032-1035 (1994).

• L. Griffith, D.E. Discher,J. Tong, and M.C. Williams. A Hydrodynamic Interpretation of Crisis in SickleCell Anemia. Microvascular Research 47:41-54 (1994).