Nanomechanics of Biological, Biomedical, Biomimetic Materials Christine Ortiz, MIT-DMSE 2004 ( I. BIOLOGICAL TISSUES ● Cartilage (J. Seog, L. Han, L. Ng, D. Dean) ● Bone (K. Tai) ● Nacre (B. Bruet, C. King, H. Qi, R. Panas) II. BIOMEDICAL INTERACTIONS ● Protein-SAMs/PEO (M. Rixman) ● Vascular Grafts (C. Macias) ● Saccharide Surfaces (J. Choi, N. Yang) ● Endotracheal Tubes (K. Brodie) ● Pharmaceuticals (R. Domike) ● Bone Implants (J. Vandiver) III. BIOMIMETIC BLOCK COPOLYMERS ● Non Stimulus Responsive P(HEMA-g-EG) (D. Zhang) ● Stimulus Responsive p(MAA-g-EG) (M. Ye)

Molecular Origins of Bio(hemo)compatibility : Materials Design Issues and Challenges at the Nanoscale CHRISTINE ORTIZ, Assistant Professor Monica Rixman, Delphine Dean, Celia Macias Department of Materials Science and Engineering, MIT WWW : c D. Breger, used w/permission,

CHRISTINE ORTIZ, ASSISTANT PROFESSOR MASSACHUSETTS INSTITUTE OF TECHNOLOGY DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERING CAMBRIDGE, MA FACTORS AFFECTING PROTEIN ADSORPTION 227th ACS National Meeting Division of Polymer Chemistry Symposium "Biomacromolecule Interactions with Synthetic Surfaces" Anaheim, CA D SURFACE COATING U=-∫F(D)dD  Initial protein adsorption will be determined by longer range, larger spatial length scale of averaged surface properties : many different attractive/ repulsive components lead to complicated interactions (Szleifer, I., 1997, Halperin, A., 1999 Leckband, D., et al., 2000)  Secondary stages of protein adsorption depend on shorter range biomolecular adhesive binding processes that take place when the protein is in close contact with the surface (*the conformation, orientation, and mobility of the adsorbed proteins, the time scale of conformational changes, protein exchange and desorption, and interactions of adsorbed proteins with each other) BIOMATERIAL

CHRISTINE ORTIZ, ASSISTANT PROFESSOR MASSACHUSETTS INSTITUTE OF TECHNOLOGY DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERING CAMBRIDGE, MA Direct Measurement of Protein Interactions with End-Grafted Poly(ethylene oxide) (PEO) Macromolecules 227th ACS National Meeting Division of Polymer Chemistry Symposium "Biomacromolecule Interactions with Synthetic Surfaces" Anaheim, CA chemically end-grafted PEO 50K “mushroom” L contour= 393 nm R F =8.7 nm F sodium phosphate buffer solution IS=0.01M pH=7.4 D lipid-bound HSA functionalized probe tip, R TIP ~65 nm (SEM) Au-coated silicon chip covalently immobilized HSA ~10 nm s = 62 ± 28 nm ~ proteins in maximum interaction area (D=0) ~2.5 PEO chains in maximum interaction area (D=0) Si 3 N 4 Rixman, et al. accepted, Langmuir 2003.

Chemical Attachment Scheme of Lipid-Bound HSA to Si 3 N 4 Probe Tip A. Vinkier; Heyvaert, I.; D'Hoore, A.; McKittrick, T.; C., V. H.; Engelborghs, Y.; Hellemans, I. Ultramicroscopy 1995, 57, 337. S. O. Vansteenkiste; Corneillie, S. I.; Schacht, E. H.; Chen, X.; Davies, M. C.; Moens, M.; Van Vaeck, L. Langmuir 2000, 16, Fluorescence micrograph of HSA-functionalized cantilever (courtesy of Irvine Lab-DMSE) probe tip location

F Au R F (PEO) magnitude of force much larger than predicted by theory Rixman, et al., Langmuir AVERAGE APPROACH CURVE : HSA PROBE TIP VERSUS PEO (SUBTRACTED AU INTERACTION) PBS, IS=0.01M, pH=7.4

HSA versus PEO : Effect of NaCl IS Approach CONCLUSION: Electrostatic double layer and configurational entropy are outweighed by another interaction which increases with IS →possibly due to water interphase layer R F (PEO) ● Salt screening : electrostatic double layer force expected↓ with ↑IS ● NaCl reduces the goodness of solvent for PEO (Armstrong, et al. 2001) : configurational entropy force expected↓ with ↑IS Rixman, et al unpublished data

HSA versus PEO : Effect of Solvent on Approach Isopropanol has been shown to block hydrophobic interaction forces (Jiang, et al 2002) R F (PEO) Rixman, et al unpublished data

CHRISTINE ORTIZ, ASSISTANT PROFESSOR MASSACHUSETTS INSTITUTE OF TECHNOLOGY DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERING CAMBRIDGE, MA ACKNOWLEDGEMENTS 50th Annual Meeting of the Orthopaedic Research Society (San Francisco, CA) Workshop on Molecular Nano-Mechanics of Extracellular Matrix of Musculoskeletal Tissues Joonil SeogDelphine DeanLaurel Ng Outside Collaborators: Dr. Anna Plaas, Shirley Wong-Palms (Shriners) Funding: Dupont-MIT Alliance, Shriners of North America, NIH AR45779 (AJG), Whitaker Foundation, Cambridge-MIT Institute Kuangshin TaiProf. Alan Grodzinsky