mechanics of nanomaterials (ae 244)

8/14/2019 Mechanics of Nanomaterials (Ae 244)

http://slidepdf.com/reader/full/mechanics-of-nanomaterials-ae-244 1/48

1

Mechanics of Nanomaterials (Ae 244)

Nano-BioMechanics



2

Overview nano-biomechanics



3




4


www.balgrist.ch



5


M. Spector, Ph.D. and I.V. Yannas, Ph.D., MIT



6

1. Identification of cell motility and orientation

2. Effect of diseases or drug chemicals on cells

3. Mechanotransduction (understanding of how cells convert mechanicalstimulus into chemical activity like hormone release, Ca signaling andprotein synthesis) EMERGING FIELD!

4. Cell differentiation, migration and apoptosis

5. Clinical diagnostics/treatment6. Biomaterials/tissues interaction

7. Cell Adhesion

8. Cell wounding/healing

9. Tissue Engineering

Relevance of Nano-biomechanics

www.nano-link.net/images/search_dom.png



7

Cell Motility/Migration

A crucial factor in cell migration is the system of forces generated during interactions of thecell with the substrate over which it moves. These interactions are influenced by surfacechemistry, topology and overall substrate compliance. Several studies have indicated that

focal adhesions (FAs) act as mechanosensors whose input feeds directly into the regulation ofphysiological processes. In order to propel itself, a cell exerts tractive forces on the substratevia its adhesion molecules. As a response, a mechanical stress is generated in the substrate.As cells probe their environment, their shape and adhesion, as well as their cytoskeletalorganization and tension, are affected and regulated by the stress at the cell/substrateinterface.

http://images.google.com/imgres?imgurl=http://www.cellmigration.org/resource/imaging/res_resources_images/ctafigure6.png&imgrefurl=http://www.cellmigration.org/resource/imaging/imaging_approaches_force_imaging.shtml&h=302&w=480&sz=324&hl

=en&start=4&um=1&tbnid=RYw_dlhi-SnasM:&tbnh=81&tbnw=129&prev=



8


Biologists and engineers have been developing cell traction assays on elastic substrates formore than 20 years. According to the mechanics of probing, the existing methods can bedivided into two conceptually different groups: continuum methods and discrete methods. Amore intuitive division according to the substrate material (silicone, polyacrylamide, or other) isoften used, but it is mentioned only parenthetically in the classification presented below.

Continuum methods. These methods of probing the cell tractions are based on recording theelastic response of the substrate as a continuum. The displacement of any point on thesubstrate is coupled with the displacements of neighboring points-- thus, the force sensor isthe entire surface of the substrate.





9


Smooth muscle cell lying on a bed of microneedles (bar = 10 µm): a) sketch of the

idea behind the method (d = 2-10 µm, L = 3-50 µm, spacing = 6-10 µm); b) SEM ofthe cell deforming the posts during adhesion; c) traction map overlaid with theconfocal image of immunofluorescence staining of the cell, with FA protein vinculinstained green. (adapted from Tan et al., 2003).



10




11


Discrete methods. These methods are based on probing the cell tractions at discrete pointsat the cell/substrate interface--thus the designation "discrete" in classification of the method.

The first notable substrate of the discrete kind was based on micro-electro-mechanical system(MEMS) devices (Galbraith & Sheetz, 1997), micromachined from a silicon wafer and coated

with laminin. The substrate contains arrays of micro-cantilevers each tipped with a 4-25 µm2

pad. Each cantilever is deflected by the cell as it sweeps over the pad and the magnitude ofdeflection, as well as the direction in which the cell moved are recorded. The Beam Theory,with its simple algebraic equation of proportionality between the force and cantileverdeflection, is then used to calculate the force that cell exerts on the pad. Each cantileverdeflects independently of its neighbors and allows the measurement of tractions at single

adhesion sites.

The main disadvantage, as for the micropatterned substrate, is the high cost of fabrication ofMEMS substrate. Also, the tractions can be measured only at the positions that the cell"chooses" to cross--unless the point of interest on the cell moves over one of the pads, thetraction at that location on the cell/substrate interface cannot be calculated. Therefore, the

continuum methods have an advantage over this discrete method in that they allow forcalculation of tractions at any point of the cell/substrate interface. However, this method isimpervious to the degradation of extracellular matrix (ECM) proteins conjugated to the surface,so it can be used for a wide selection of cell types.





12

Effect of diseases or drug chemicals on cells

Medical researchers have long known that diseases can cause -- or be caused by-- physical changes in individual cells. For instance, invading parasites can distortor degrade blood cells, and heart failure can occur as muscle cells lose their abilityto contract in the wake of a heart attack.

Knowing the effect of forces as small as a piconewton on a cell gives researchers amuch finer view of the ways in which diseased cells differ from healthy ones.

Translating nanoscale measurements of materials such as the thin films used inmicroelectronic components and nanomeasurement techniques to living cells is the

essence of nanobiomechanics. A new multidisciplinary area is created whenengineers work closely with microbiologists and medical researchers to learn moreabout how our cells react to tiny forces and how their physical form is affected bydisease.

"We know mechanics plays a role in disease," says Suresh. "We hope it can be used to figure out treatments." If it can, the tiny field of nanomeasurement could have a huge impact on the future of medicine.

MIT Technology review



13

Mechanotransduction

M. Spector, MIT



14

Biomaterials/tissues interaction

M. Spector, MIT



15

Identification of cell motility and orientation



16




17




18

Cell wounding/healing

M. Spector, MIT



19




20




21

Tissue Engineering

In 1997 Dr Jay Vacanti grew ahuman ear from cartilage cells the

back of a mouse



22

“Living cells possess structural and physical properties that enable them to withstand the physiologicalenvironment as well as mechanical stimuli occurring within and outside the body. Any deviation from these

properties will not only undermine the physical integrity of the cells, but also their biological functions. As such,a quantitative study in single cell mechanics needs to be conducted.”

Cell Mechanics

Mechanical models that have been developed to characterize mechanical responses of living

cells when subjected to both transient and dynamic loads:- The cortical shell–liquid core (or liquid drop) models which are widely applied to suspended

cells;

- the solid model which is generally used for adherent cells;

- the power-law structural damping model which is more suited for studying the dynamicbehavior of adherent cells;

- and finally, the biphasic model which has been widely used to study musculoskeletal cellmechanics.

Relevant factors to be addressed:

1. Structural heterogeneity,

2. appropriate constitutive relations for each of the distinct subcellular regions andcomponents, and

3. active forces acting within the cell.

C.T. Lim, Review, Journal of Biomechanics 39 (2006) 195–16



23

Cell Mechanics




24

Experimental methods and associated models



25

Micropipette aspiration experiments




26

Newtonian Liquid Drop Model



27

Compound Liquid Drop Model



28

Maxwell Liquid drop model



29

Linear Elastic solid model



30

The homogeneous standard linear viscoelastic solid (SLS) model:



31

OPTICAL TWEEZERS Experiments

An optical tweezer is an instrument that uses a focused laser beam to providean attractive or repulsive force, depending on the index mismatch (typically onthe order of piconewtons) to physically hold and move microscopic dielectricobjects. Optical tweezers have been particularly successful in studying avariety of biological systems in recent years.

wikipedia



32

OPTICAL TWEEZERS Experiments

Optical tweezers stretch a healthy red blood cell (top row), increasing theapplied force slowly, by a matter of piconewtons. A cell in a late stage ofmalarial infection is stretched in a similar fashion (bottom row). Theexperiment illustrates how the infected cell becomes rigid, which prevents

it from traveling easily through blood capillaries and helps cause thesymptoms of malaria.

S. Suresh, MIT



33

OPTICAL TWEEZERS



34

RED BLOOD CELLS FLOW MECHANICS

MOVIE BORROWED FROM the “Bioelectronics” class thought by Prof. Michael J. Heller,University of California San Diego, Departments Bioengineering/Electrical and Computer

EngineeringEngineering



35

RED BLOOD CELLS FLOW MECHANICS

MOVIE BORROWED FROM the “Bioelectronics” class thought by Prof. Michael J. Heller,University of California San Diego, Departments Bioengineering/Electrical and Computer

EngineeringEngineering



36

MULTISCALE APPROACH for Mechanotransduction



37

AFM Experiments

Principles: The atomic force microscope (AFM) is so named because it measures forces thatare governed by the interaction potentials between atoms. Depending on the sample and tipmaterial and the medium in between different interactions will be important. Always present arevan der Waals interaction and very short range repulsive interaction. Van der Waals forces aregenerally attractive (except for very rare cases) and can be sensed at distances of 10 Å and

more.In biological samples many other interaction may also be present such as electrostaticinteractions (attractive and repulsive), steric interaction (e.g. with polymers, always repulsive)and specific adhesion forces at molecular contact. All these forces are usually called colloidalforces (Israelachvili, 1992). Measurements of these forces are made by means of the AFM

probe, a sharp tip that interacts with the sample surface.Typical forces between the tip and the sample are within the range of 10 p - 10 nN in liquidsalthough this also depends on the size of the tip used. The tip is mounted on the end of a soft,silicon nitride cantilever spring and it's position in relation to the sample is controlled with highprecision in X, Y and Z using tube-shaped piezoceramics. Where optical setups are combined

with the AFM it is the cantilever which translocates, alternatively the whole sample is mountedon a piezoelectric scanner and moved with respect to the probe.



38

AFM Experiments

The spontaneous beating of live myocyte cells can be monitored directly by AFM.The bottom most spindle like cell is a myocyte, the neighboring cell above withprominent cytoskeletal structures is a fibroblast. When positioning the AFM tip to agiven location (yellow dots) we can follow the height of the cell as a function of time

(red traces). (from: Domke et al., 1999.)



39

NANOPORE (ION CHANNELS) MECHANICS



40





41


TISSUE AGING d CRACKING



42

TISSUE AGING and CRACKING

“The changes in the mineralization suggested a simple mechanism of mineral

‘dissolution and reprecipitation’, while examination of the collagen revealed incipientdamage in the form of voids within the collagen fibers. These studies help shed lighton the process of aging and fracture of mineralized tissues and are useful steps indeveloping a framework for understanding such processes.”

TISSUE AGING d CRACKING



43





44


FIB + TEManalysis




45





46


TISSUE and other BIOMATERIALS Characterization



47





48


mechanics of nanomaterials (ae 244)

Documents