Lecture 10.(Biophysics_2_2026.pdf) ) Biophysics 2 and Cardiac Tissue Engineering

The majority of growth and remodelling of the vascular network takes place when

blood circulation has already initiated

What does flow velocity lead to in at the endothelial cells

shear stress: parallel to the tissue surface, depends on the flow rate, viscosity geometry of the tube

What does pressure lead to in at the endothelial cells

Circumferential (tangential) and axial stress (along the long axis of the vessel)

What is the equation of conservation of momentum

delta p = u delta² u

What is the equation of conservation of mass

delta u = 0

What is the equation for the boundary conditions from wall dynamics

u|sigma = ub

What can the application of flow velocimetry to cell/tissue dynamics be used for

• PIV can be used to tissue flows/deformations

• Cell tracking (based on nucleolus market)

What are the key concepts of cell mechanics

• cell junctions

• cell flows

• minimal cell models: vertex models

• solid-fluid transitions of tissues

What are the cell mechanics of epithelial cells

• apico-basal (different sets of proteins/structures in the apical and basal regions)

• basal interfaces adhere to ECM (focal adhesions)

• cells adhere to each other through adhesion molecules (cadherins, bound, indirectly, to an actomyosin network)

• Actomyosin cytoskeleton: actin filaments myosin molecular motors: strongly concentrated near the cell membrane, allowing cells and tissues to deform

• Two-dimensional models provide good phenomenology

Cell matrix adhesion

focal adhesions, integrins link the cell to the extracellular matrix (ECM) and transmit mechanical forces

Adherens Junctions

connects actin filaments of neighbouring cells; maintain structural integrity hold cells together

Adhesion molecule

cadherin

mechanosensing proteins:

talin, vinculin and myosin-II, a-catenin

What happens to the ATP under mechanical stress

Under mechanical stress, ATP released through channel protein Pannexin-1 activates purinergic receptors in the neighbouring cells to regulate cell tension

What do tissue-level and cell-level studies show about the mechanics of epithelial cell layers?

Epithelial cell layers behave as mechanically integrated tissues, but their deformation can also be understood at the level of individual cell shape changes

What tools can be used to quantify cell shape from microscopy images

cell pose (based on pretrained neural network models), cell profiler, image J, matlab and payton libraries

What tools can be created for segmentation output

cell masks (the intensity of the pixels within a cell are set to a constant ID value). Cell boundaries can then be extracted; cell orientation/elongation can be quantified

What is cell intercalation

• change in neighbouring cells can be driven

• forces: both extrinsic (applied by other cells or stretcher), or/and intrinsic (actomyosin)

• contributes to viscoelasticity of epithelial tissues; region specific

• solid to fluid transitions

• fluidity allows tissue remodelling

• solid state: tissue establishment/maintenance

What is the equation for a network of vertexes that move under a force

Fu=- vector ru EVM

What is the equation for shape factor

po =Po/sqrt(Ao)

What is the monolayer tissue growth in vitro

• originally used to study the spread of a favoured gene through a population

• good model for expansion of an in vitro monolayer cell colony due to proliferation and cellular migration

• low n densities proliferation is approximately exponential, with linear growth rate r n

• Approaching N, inhibition of proliferation rate

What is the Fisher’s equation

differential n/ differential t = rn (N-n) +D vector² n

What is the Fisher’s equation that includes motility

rn(N-n)

What mechanical forces do endothelial cells experience from blood flow?

Shear stress, Circumferential stress, Axial stress

What determines shear stress in a vessel?

Shear stress depends on:

• flow rate

• viscosity

• vessel geometry

What equations are central in an in silico fluid model?

• Conservation of momentum

• Conservation of mass
  plus boundary conditions from wall dynamics.

What does EHT stand for?

Endothelial-to-hematopoietic transition.

Where does zebrafish EHT occur in this lecture example?

In cells from the ventral wall of the dorsal aorta.

What mechanical cue is important for EHT?

Circumferential stress caused by pulsatile blood flow.

How are hematopoietic progenitors extruded during EHT?

By actomyosin contraction in the endothelium.

How do cultured endothelial cells usually orient under flow?

They usually elongate along the flow direction.

How do endothelial cells orient under cyclic strain?

They tend to re-orient perpendicular to the axis of strain.

What is one example showing mechanics in pathfinding?

RGC axons sense a stiffness gradient and grow toward softer tissue, involving Piezo1.

What is microaspiration?

A method where negative pressure pulls a cell or tissue into a narrow channel to measure mechanics.

What can microaspiration measure?

It can estimate modulus/compliance from:

• channel geometry

• applied pressure

• displacement into the channel
  

What are the two main imaging velocimetry methods mentioned?

• Particle tracking (PT)

• Particle image velocimetry (PIV)

What is particle tracking?

Tracking individual particles over time; it is accurate but computationally expensive.

What kind of approach is particle tracking?

A Lagrangian approach

What is PIV?

A method that tracks ensembles of particles to estimate velocity fields.

What kind of approach is PIV?

An Eulerian approach.

What is one limitation of PIV?

It may struggle with unsteady flows or sharp gradients.

How can optical tweezers be used in flow studies?

By measuring the displacement of a trapped particle from the trap center to estimate flow.

What limits optical tweezers velocimetry?

It requires optical access and only works for low drag forces.

What does traction force microscopy measure?

The traction forces cells apply to a substrate.

How does traction force microscopy work?

It infers substrate deformation from movement of:

• embedded microbeads/nanobeads

• or micropatterns such as micropillars

How does optogenetic control of RhoA affect contractility?

• Recruit optoGEF-RhoA to membrane → increase contractility

• Sequester it at mitochondria → decrease contractility

What are the main adhesion systems in epithelial cells?

• Focal adhesions to ECM

• Cadherin-based junctions between cells

What is laser ablation used for in tissue mechanics?

To estimate junctional tension from the relaxation/recoil after ablation.

What does cell segmentation allow you to quantify?

It allows extraction of:

• cell boundaries

• orientation

• elongation

• shape metrics

What do ferrofluid microdroplets measure?

They probe tissue mechanics:

• fast time constant → elastic response

• slow time constant → viscous/dissipative response

What is cell intercalation?

A neighbor exchange process that contributes to tissue viscoelasticity, remodeling, and solid-to-fluid transitions.

What is the key idea of vertex models?

They model epithelial tissues as networks of moving vertices, with mechanics depending on cell area, perimeter, elasticity, and line tension.