SINGLE CELL MECHANICSCLASSIFICATION OF INTRA- AND INTERMOLECULAR FORCESSPECIFIC TYPES OF INTRA- AND INTERMOLECULAR FORCESHYDROPHOBIC ("WATER FEARING") INTERACTIONSNONCOVALENT INTERACTIONS IN FOLDED PROTEINSSELF-ASSEMBLING PEPTIDE AMPHIPHILES FOR REGENERATIVE MEDICINE3.052 Nanomechanics of Materials and Biomaterials Tuesday 03/06/07 Prof. C. Ortiz, MIT-DMSEILECTURE 8: INTRODUCTION TO INTRA- ANDINTERMOLECULAR FORCESOutline :LAST TIME : SINGLE CELL MECHANICS.................................................................................................2CLASSIFICATION OF INTRA- AND INTERMOLECULAR FORCES ........................................................3SPECIFIC TYPES OF INTRA- AND INTERMOLECULAR FORCES.........................................................4HYDROPHOBIC / HYDROPHILIC INTERACTIONS..................................................................................5EXAMPLES.............................................................................................................................................6-7 Biological : Noncovalent Interactions in Folded Protein Structures...............................................6 Synthetic : Self-Assembling Peptide Amphiphiles for Regenerative Medicine..............................7 Objectives: To explore the qualitative origins of intra- and intermolecular forces Readings: Course Reader documents 16-19, Links on "Supplementary Resources" section of Stellar (Optional)Multimedia : Protein folding demo posted on stellar; Lecture 8 : Bonding and protein structure (California Lutheran University)13.052 Nanomechanics of Materials and Biomaterials Tuesday 03/06/07 Prof. C. Ortiz, MIT-DMSESINGLE CELL MECHANICS-single cell AFM imaging-motivation (musculoskeletal tissue, circulatory system, brain)-experimental methods 1) localized area of the cell is deformed AFM, magnetic bead, 2) mechanical loading of an entirecell micropipette aspiration, optical trap, 3) simultaneous mechanical loading of a population of cells (shear flow, cell forcemonitor)-cell modeling (Dao, et al 2003 J. Mech. Phys. Solids.)• The composite is modeled as an isotropic, elastic, continuum, incompressible (constant volume), constant surface areaConstitutive Law : stress vs. strain relationship that describes a particular materialSingle macromolecule Gaussian linear elastic Hookean spring F=kr → summing over a network of random coil molecules"Triangulated Network"[1] Mohandas, et al. Mechanical properties of the red cell membrane in relation to molecular structures and geneticdefects. Annu. Rec. Biophys. Struct. 1994. 23:787-818{( ) ( )l +l +l + l +l +ll1 4 4 442 4 4 4 431 4 4 442 4 4 4 4332 3 2 2 3 2o1 2 3 3 1 2 3Strain energy of a 3D rubber elastic networknonGaussian Nonlinear Strain Hardening TermNeo-Hookean Rubber ElasticitryGU = - 3 C - 32= extension or stretch ra( )( )( )( )( )( ), ,l l l=�s�ll l lff31 21 2 3o o o1 2 3o2n11 2 3LL Ltio, = = =L L LG shear modulus by definitionUuniaxial normal stress, ( N/m ) =constant volume constraint = from definition of extension ratio & geometry23.052 Nanomechanics of Materials and Biomaterials Tuesday 03/06/07 Prof. C. Ortiz, MIT-DMSECLASSIFICATION OF INTRA- AND INTERMOLECULAR FORCES (within individual molecules) (between individual molecules)-Definitions : Interaction (more general), force (push or pull), bond (the attraction between atoms in a molecule or crystalline structure)→ all intra- and intermolecular forces are electrostatic in origin → key to life on earth (e.g. water, cell membranes, protein folding, etc.)-strength measured relative to the thermal energy (room temperature) : kBT= 4.1 ● 10-21 J : "ruler" noncovalent 1 4 4 4 442 4 4 4 4 43I.Primary or Chemical● individually strong > kBT ● outer orbital e- shared that the discrete nature of the atom is lost● quantum mechanical in origin● covalent → possess specificity, directionality, stoichiometry● metallic → delocalized electrons 1 4 4 4 442 4 4 4 4 43covalent, metallic, ionic (in air)II. Secondary or Physical● individually weak ≤ kBT ● no e- sharing; between two or more atoms so discrete nature of atoms preserved● more subtle attraction in origin between (+) and (-) charges typicallylack specificity, directionality, stoichiometry 1 4 4 4 442 4 4 4 4 43ionic (in water), polar,polarization, dispersionIII. "Special" ● broad range of strength● controversial● not a "true" bond 1 4 4 4 442 4 4 4 4 43hydrophobic, hydrophilic,polymer effects (e.g. excludedvolume, entropic elasticity),electrostatic double layer)- Biological systems and bottom-up self-assembly is based on the balance and interplay of intra- and intermolecular forces.33.052 Nanomechanics of Materials and Biomaterials Tuesday 03/06/07 Prof. C. Ortiz, MIT-DMSE-Noncovalent interactions allow for dynamic systems, i.e. breaking reversible reforming bonds doesn't require much energy)/individually weak, forces are cumulative → stable in parallel.SPECIFIC TYPES OF INTRA- AND INTERMOLECULAR FORCES Ionic-Coulombic attraction between oppositely charged species-individually strong, however greatly weakened in the presence of water (e.g. center of proteins→strong, DNA-proteins)Polar Interactions polar = asymmetric distribution of charge● attractive force between an ion and a permanent dipole or two permanent dipoles where the (+) charge attracts (-) (e.g. hydrogen bonds)(-all 3 atoms in water can H-bond, up to 4 per molecule, important in biology because it is able to form weak interactions with so many different chemical species)Polarization Interactions● an ion or dipole in the vicinity of a nonpolar atom or molecule causes an instantaneous polarization and electrostatic attraction43.052 Nanomechanics of Materials and Biomaterials Tuesday 03/06/07 Prof. C. Ortiz, MIT-DMSElarger the e- cloud easier to distort (> polarizability)London Dispersion ● nonpolar-nonpolar and induced dipole - induced dipole● charge fluctuation, the (+) nucleus of a nonpolar atom attracts the (-) charged electron cloud of another nonpolar atom → an instantaneous induced, short lived fluctuating dipole, -takes place in all atoms / molecules,HYDROPHOBIC ("WATER