Nanomechanics of Biological, Biomedical, Biomimetic Materials

Christine Ortiz, MIT-DMSE 2004 (http://web.mit.edu/cortiz/www)

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, MITWWW : http://web.mit.edu/cortiz/www

c

D. Breger, used w/permission, http://www.ldeo.columbia.edu/micro/images.section/pages/bloodclot.html

CHRISTINE ORTIZ, ASSISTANT PROFESSORMASSACHUSETTS INSTITUTE OF TECHNOLOGY

DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERINGCAMBRIDGE, MA 02139

FACTORS AFFECTING PROTEIN ADSORPTION227th ACS National Meeting Division of Polymer Chemistry

Symposium "Biomacromolecule Interactions with Synthetic Surfaces" Anaheim, CA 2004.

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., 1999Leckband, 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 PROFESSORMASSACHUSETTS INSTITUTE OF TECHNOLOGY

DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERINGCAMBRIDGE, MA 02139

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 2004.

chemically end-grafted

PEO50K “mushroom”Lcontour= 393 nm

RF=8.7 nm

F

sodium phosphate

buffer solutionIS=0.01M pH=7.4

D

lipid-bound HSA functionalized probe tip, RTIP~65 nm (SEM)

Au-coated silicon chip

covalently immobilized HSA

~10 nm

s = 62 ± 28 nm

~35-190proteins in maximum interaction area (D=0)

~2.5 PEO chains in maximum

interaction area (D=0)

Si3N4

Rixman, et al.

accepted, Langmuir 2003.

Chemical Attachment Scheme of Lipid-Bound HSA to Si3N4 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, 3330.

HSAHSA

Si OH

II

OO

NH2

NH2H2N

III

H3C O Si

CH3

CH3

NH2

ABDMS

Si NH2

Si NH2

Si O Si NH2

CH3

CH3

NH2

NH2

Glutaraldehyde

+

Si3N4 Probe Tip

N

Si NH2

Si NH2

Si O Si N

CH3

CH3

SiN

SiN

Si O Si N

CH3

CH3

O O

OO

O

SiN

O O

SiN

OO

I

Fluorescence micrographof HSA-functionalized

cantilever (courtesy of Irvine Lab-DMSE)

probe tip

location

-0.8

0.2

1.2

2.2

3.2

4.2

0 5 10 15 20 25 30

Distance (nm)

For

ce/ R

adiu

s (m

N/m

)

-0.05

0.05

0.15

0.25

For

ce (nN

)

HSA probe tip versus PEOsurface averageElectrostatic surface chargemodel neutral surfacevan der WaalsPEO/ HOH/ HSADolan Edwards steric

F

Au

RF (PEO)

• magnitude of force much larger

than predicted by theory

Rixman, et al., Langmuir 2003.

AVERAGE APPROACH CURVE : HSA PROBE TIP VERSUS PEO (SUBTRACTED AU INTERACTION) PBS, IS=0.01M, pH=7.4

0

0.5

1

1.5

2

2.5

3

3.5

0 10 20 30Distance (nm)

For

ce/R

adiu

s (m

N/m

)

0

0.05

0.1

0.15

0.2

0.25

0.3

For

ce (nN

)

0.15M

1.0M

0.01M

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

RF (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. 2003 unpublished data

HSA versus PEO : Effect of Solvent on ApproachIsopropanol has been shown to block hydrophobic interaction

forces(Jiang, et al 2002)

RF (PEO)

Rixman, et al. 2003 unpublished data

-7

-5

-3

-1

1

3

5

0 10 20 30

Distance (nm)

For

ce/R

adiu

s (m

N/m

)

-0.32

-0.22

-0.12

-0.02

0.09

0.19

Force (nN

)

0% Isopropanol0.5% Isopropanol5% Isopropanol100% Isopropanol0% F+sd0% F-sd0.5% F+sd0.5% F-sd5% F+sd5% F-sd100% + sd100% - sdSeries1

CHRISTINE ORTIZ, ASSISTANT PROFESSORMASSACHUSETTS INSTITUTE OF TECHNOLOGY

DEPARTMENT OF MATERIALS SCIENCE AND ENGINEERINGCAMBRIDGE, MA 02139

ACKNOWLEDGEMENTS50th Annual Meeting of the Orthopaedic Research Society (San Francisco, CA)

Workshop on Molecular Nano-Mechanics of Extracellular Matrix of Musculoskeletal Tissues

Joonil SeogDelphine Dean Laurel 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