1. RESEARCH PROGRAM OF CHRISTINE ORTIZ Multiscale Approach: single molecules →biomimetic assemblies → matrix of single cells → in-tact tissue Musculoskeletal (internal to the body) (e.g. cartilage, bone, etc.) Exoskeletal (external to the body) (e.g. gastropod molluscs, armored fish, etc.) Engineering motivation: -Bio-inspiration and guidance for improved materials for protective and structural applications Medical motivation: -to facilitate the development of improved clinical treatments for disease & injury through tissue repair and/or replacement→ regenerative medicine / tissue engineering -nanoscale forces and displacements (F,  ), constitutive laws (  ) -local, spatially-specific material properties (E,  Y, H, energy dissipation, etc.) -molecular-level structure-property relationships -novel mechanical phenomena (e.g. nanogranular friction, fracture localization, etc.) Objective : A Fundamental, Mechanistic-Based Understanding of Tissue Function, Quality, and Pathology NANOMECHANICS OF STRUCTURAL BIOLOGICAL MATERIALS

2. SELECTED RECENT ACCOMPLISHMENTS (MUSCULOSKELETAL) ● Prior to tenure: established the use of nanomechanics in near-physiological conditions applied to healthy musculoskeletal tissues ● Post-tenure: application of nanomechanics to the field of tissue engineering; temporal evolution of the quasistatic mechanical properties (Ng+ J. Biomech. 2007) and dynamic visco(poro)elasticity (Lee+ J. Biomech. 2009) of the tissue engineered cartilage matrix associated with individual cells  ● Assessment of engineered tissue quality and heterogeneity locally at unprecedented resolutions as a function of cell type, scaffold, growth factors, etc. ● Relevance to mechanotransduction COLLABORATORS ● A.J. Grodzinsky (MIT-BE), D. Gazit (Hebrew U.) RESEARCH PROGRAM OF CHRISTINE ORTIZ NANOMECHANICS OF STRUCTURAL BIOLOGICAL MATERIALS viscoelasticity + poroelasticity (Buschmann+) 10 µm chondrocyte, stem cell AFM colloidal tip matrix

3. RESEARCH PROGRAM OF CHRISTINE ORTIZ NANOMECHANICS OF STRUCTURAL BIOLOGICAL MATERIALS FEA  =15 º, c =100 MPa SELECTED RECENT ACCOMPLISHMENTS (MUSCULOSKELETAL) ● Prior to tenure: established the experimental and theoretical methods for high resolution imaging and nanomechanics of bone ● Post-tenure Postulated a new theory for the strength on bone involving "nanogranular friction" (Tai+ Nano Lett., 2006, featured in Nat. Nanotech. News and Views, 2006, commentary; J. Am. Acad. Ortho. Surg. 2007); discovered a new energy dissipation mechanism in mineralized biological tissues; nanoscale heterogeneity (Tai+ Nat. Mater. 2007)→assessed nanoscale properties of stem cell-based tissue engineered bone (Tai+ J. Biomech., Pelled+ Tiss. Eng. 2008).  ● Understanding the mechanisms that prevent our bones from fracturing under physiological loading will aid in the treatment of problems that result from old age, disease, and injury. COLLABORATORS ● F. Ulm (MIT-CEE), S. Suresh (MIT-DMSE), D. Gazit (Hebrew U.)

4. RESEARCH PROGRAM OF CHRISTINE ORTIZ NANOMECHANICS OF STRUCTURAL BIOLOGICAL MATERIALS penetration on top of fish scale Ganoine Dentin Isopedine Bone 10 μm cross section of fish scale SELECTED RECENT ACCOMPLISHMENTS (EXOSKELETAL) ● Prior to tenure: established an experimental and theoretical framework for studies of mineralized biological materials at the nanoscale, using nacre as a model system ● Post-tenure Determined multilayered design (i.e. thickness, sequence, and material properties of individual layers) of a natural armor which facilitate circumferential fracture and prevent interfacial delamination under a penetrating load (bite from predator) in order to localize impact and prevent catastrophic failure (Bruet+ Nat. Mater. Cover 2008, Wang+ JMR 2009, Yao+ PNAS, 2009)  ● Bio-inspiration and guidance for improved materials for protective and structural applications (Ortiz & Boyce Science 2008) COLLABORATORS ● M.C. Boyce (MIT – MechE), D. Gazit (Hebrew U.)

5. SELECTED RECENT ACCOMPLISHMENTS (EXOSKELETAL) ● Defense Science Study Group (DSSG) 2008-2009 ● Department of Defense National Security Science and Engineering Faculty Fellows: NSSEFF (468 white papers resulted in 17 semifinalists being invited to submit full proposals and in person interviews → 10 awardees selected)→ $4.6M total ● MIT Institute for Soldier Nanotechnologies (Grantee, 2002-present) ● Raytheon, Inc. RESEARCH PROGRAM OF CHRISTINE ORTIZ NANOMECHANICS OF STRUCTURAL BIOLOGICAL MATERIALS l1l1 l2l2 l3l3 l4l4  (  ) 1  (CTE) 1   durable functionally graded interphases − mitigates delamination multilayered design (layer thickness, sequence) − penetration resistance, minimizes back-deformation into soft tissue, prevents catastrophic fracture (self-healing), thermal management, weight reduction interlocking articulation at reinforced joints anisotropic constitutive models of individual layers − local stress distributions curved geometry (shape / size) of individual armor units – energy absorption, ergonomics RtRt lili tissue finite viscoelastic deformation (damage tolerance) z anisotropic spatial arrangement of armor units – cooperative deformation of entire body biomechanical flexibility MOBILITY PROTECTION ()t()t geometry and mechanical properties of threat (e.g. penetrating indenter) RuRu  (  ) 2  (CTE) 2    (  ) 3  (CTE) 3    (  ) 4  (CTE) 4   unique organic-inorganic nanocomposite morphologies (e.g. fibrous, prismatic, nacreous etc.) - energy dissipation camouflage pigmentation back deflection 4 Sub-Programs a) Flexible natural armor b) Transparent natural armor c) Natural armor for blast d) Natural armor for extreme environments (deep sea)