This document contains the lecture notes of the course Cell Mechanobiology and Engineering, with the exception of lecture 1 as this was only an introduction lecture. Notes from all other lectures (2 to 14) are concluded.
Cell mechanobiology and engineering 8MM40
Lecture 2 – Cell and ECM mechanics
Cell mechanics
Physical forces (either exerted or sensed by the cells) (1) influence cell behaviour such as: growth,
differentiation, metabolism, secretion, movement and gene expression, and hence (2) influence the
function and architecture of all living tissues.
The cell response to mechanical forces results in functional adaption, damage or pathologies. The tissues
recognize forces which are then transmitted to cell level, for example growth of muscle tissue as response
to exercise.
• Positive responses: endothelium reorganisation, muscle adaption, bone remodelling
• Negative responses: atherosclerosis, hearing disorders, pressure ulcers, cardiac overload
Ex. pressure ulcer: when person lies down or sits down for long time due to disability, constant pressure
on certain area. Pressure is mechanical cue for cells, this leads to pressure ulcers which leads to further
degeneration of tissue.
Diseases that influence cell mechanics
• Chronic hypertension (hemodynamic overload) induces increased cell volume, specific signal-
transduction pathways and altered gene expression in myocytes
• Emery Dreyfuss muscle dystrophy is associated with abnormalities in nuclear organisation, which
may result in decreased nuclear stiffness and strength and early nuclear damage.
• Pompe’s disease results in impaired force transmission in muscle fibers.
Examples of how cell mechanics does not work right in the body.
Relevance & applications of cell mechanics
Alterations in the mechanical properties of cells or the interactions between the cell and its environment
may cause changes in cell and tissue behaviour and architecture eventually leading to functional adaption
or pathological conditions
• Mobility of cancer cells
• Survival of cells
• Treatment of mechanical diseases in skeletal and heart muscle
• Bone structure rearrangement
• Ciliar movement diseases
• Intracellular molecular transport
• Gene therapy
Natural SI unit
• Natural SI unit for force at level of the cell is μN, nN or pN, depends on what you are looking at.
pN for force generated by single actin filaments (soft cells), nN for forces at addition complexes
(stiff cells) and μN for forces generated by whole cells.
• Natural SI unit for length at level of the cell is μm
• Natural SI unit for (protein) concentration μM
• When material is deformed to 110% of its original length, stretch and strain defined as: stretch =
1.1 and strain = 0.1
1
,Cell culture
• Isolate cells
• Various cell sources
o Primary
o Continuous
o Cloned
• Growing in culture
• Cell culture facilities
• Cell manipulation & mechanical testing. With in vitro culture you can directly manipulate cells and
test them mechanically.
Cells differ in many details according to function, evolution and environment (>200 cell types in human).
The many different types of cell have different properties and mechanical behaviour and require
different representations.
For cancer cells: the stiffer the cell line is, the less invasive it is.
Mechanically important cellular components
Mechanical properties of the whole cell are dependent on what the whole cell is composed of. Especially
important for determining mechanics of cell:
• Nucleus
• Cell membrane (+ cortex)
• Cytoplasm
• Cytoskeleton
Nucleus
• Stores genetic information of cell
• It is a mechanical, physical entity within the cell. It is the stiffest component of the cell.
• Underneath the nuclear envelope there is a scaffold called the nuclear lamina, this provides
structural integrity for the nucleus. If this is damaged the mechanical properties of the nucleus is
compromised. Genetic basis of family of diseases called laminopathies.
The nucleus senses mechanical signals and accordingly modulate the transcription machinery by changing
chromosome positions, chromatin arrangements and transport of molecules across the nuclear
membrane. In other words: nucleus can sense mechanical signals transduce these mechanical signals
to biochemical signals inside the cells results in cell response and behaviour.
Nucleus deformability is limiting in cancer cell migration, it is too stiff.
2
,Cell membrane (+ cortex)
• Physically separates the aqueous extracellular environment and the aqueous
cytoplasm.
• Cell membrane is a lipid bilayer
• Components: fatty acids and phospholipids
• Deformation of bilayer exposes hydrophobic part to water (energetically
unfavourable), so membrane exhibits inherent resistance to stretch. But no
inherent resistance for bending.
• Lipid molecules are mobile within bilayer no inherent resistance to
membrane bending.
• Cell maintains its structure using reinforced membrane strategy: Right underneath the cell
membrane, the cells form a thin layer of cytoskeleton called actin cortex.
The lipid bilayer on the cells are ruffled where a lot of lipid molecules are
stored. It serves as a reservoir of lipid molecules such that if it is necessary
for a cell to expand in volume, the cell membrane does not get ruptured.
There is a reservoir so that it can be stretched out.
Cell membrane is dynamic. The lipid bilayer has some kind of tension
as it does not like to be stretched and just underneath this layer is the
cortex. So, there is a balance between membrane tension and cortical
tension. This governs cell blebbing: when a part of the cell cortex is
damaged, then there is pressure difference between inside of cell and
outside so that area bubbles up. The cell can recognize that there is
damage, it forms a new cortex in the bleb, which then retracts and
eventually the full bleb retracts in. Blebs can be useful for cell migration.
Cytoplasm
• Contains cytosol and the cytoskeleton
• Is something in between water and gel
• It is viscoelastic
Viscoelasticity: exhibits both elastic and viscous properties upon deformation.
• Elastic: when you stretch it and when you release the force it bounces back.
• Viscosity: tells you how much the material flows.
So when you apply force on it, it will deform it elastically and at the same time it flows. But it does not
immediately snap back as it has viscosity as well.
Viscoelasticity can be quantified with rheometer, it allows you to apply a
controlled shear stress and shear strain. You apply deformation or stress in
sinusoidal profile.
• When you apply this to elastic material, it will immediately deform.
• When you apply this to viscous material it will deform slowly.
The time delay (δ) of the material response will determine what type of
material it is. If the time delay is zero, it is an elastic material. If the time
delay is such that the response is completely out of phase of what you are
applying, you have a complete viscous material.
3
, Elastic modulus (G’), also called storage modulus and viscous modulus (G’’),
also called lost modulus are obtained from this measurement. These can be
looked at, at different frequencies. If, for example, G’ is higher at low
frequency (when deformation is applied slowly) then at that frequency the
material acts more as elastic material and G’’ is higher at high frequency
(when deformation is applied quickly), then at that frequency the material
acts more as viscous material.
A higher viscosity indicates that medium is thick flowing,
a lower viscosity that it is thin flowing.
Cytoskeleton
• Important load-bearing structure
• Governs cell shape, motility and transport
• >8% of human genome encodes for cytoskeleton
3 major skeletal proteins:
• Actin: 6-10 nm in diameter
• Intermediate filaments, 7-11 nm
• Microtubules, 25 nm
Persistence length is reliable measure to quantify how stiff something is. Many
biomaterials and biopolymers are ‘soft matter’: can be deformed by thermal energy. For
example, if you heat up water and put spaghetti in, it changes from stiff to flexible.
The thermal energy allows particle to move around. It is related to how hot it is.
Persistence length is used to describe the stiffness or flexibility of a rod. It
is dependent on temperature and is defined as the length along a rod over
which its direction becomes nearly uncorrelated. (Li et al.,2010)
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