Title: A Computational Framework for Individual Cell-based Models from Yeast Sorting to Red Blood Cell Mechanics and Beyond
Other Titles: Een computationeel platform voor individuele cel-gebaseerde modellen van zelforganizatie bij gist over mechanica van rode bloedcellen tot een generisch celmodel
Authors: Odenthal, Tim
Issue Date: 13-Dec-2013
Abstract: The functioning of a biological tissue in many cases crucially depends on the mechanics at the cellular scale. This is shown in several example systems. Firstly, for a system of two phenotypes of yeast cells, which are adhesive and non-adhesive respectively, sorting occurs yielding a structure, in which the more adhesive cells are on the inside whereas the non-adhesive cells are on the outside. The YoungÂ’s modulus of the two strains was measured in atomic force microscopy experiments showing no difference between the strains. Compared to the results of an individual cell-based model it is found that the difference in adhesion in combination with Brownian motion and the locality of growth of new cells suffices to explain the emergence of this shell-like structure.In a second case, it is shown that the dynamics of initial cell spreading can be understood as a result of adhesion and dissipative forces at work on the interface of the developing contact plane. Especially for red blood cells, the model perfectly captures the experimental observations of two distinct experiments from the literature. A new deformable cell model with mechanistic contact interactions has been introduced to capture the developing adhesive contact. This model can be generalized to other cell types and applications in the field of individual cell-based models. To simulate these and a wide variety of similar models, a C++ software platform with a python interface has been developed and its usefulness proven by above mentioned examples. It has been more widely applied together with colleagues to develop models for microcarrier cell expansion and a new formulation of the smoothed particle hydrodynamics method for low Reynolds numbers called NSPH.
Table of Contents: Abstract
List of Figures
List of Tables
1 Introduction
1.1 Why develop a framework for computational cell mechanics?
1.2 Simulation techniques on the cellular scale
1.2.1 Mesh-based methods
1.2.2 Mesh-less methods
1.3 Goals of the framework for computational cell mechanics
2 Measuring mechanical properties of materials on the cellular scale
2.1 Micropipette Aspiration
2.1.1 Results of MA trials in Exeter
2.1.2 Conclusions micropipette aspiration
2.2 Optical tweezers
2.3 Atomic Force Microscopy
2.3.1 Young’s Modulus of Saccharomyces Cerevisiae
2.3.2 Adhesion measurements
2.4 Summary and conclusions on the measurements performed
3 Yeast cell sorting and evolutionary implications
3.1 Yeast sorting model structure
3.1.1 Equation of motion
3.1.2 Contact Mechanics
3.1.3 Budding and Growth
3.1.4 Model parameters
3.2 Measuring yeast cell sorting
3.2.1 Centres of mass
3.2.2 Radial distribution function
3.2.3 Coordination number
3.2.4 Cluster analysis & compaction
3.3 Results and Discussion of yeast sorting simulations
3.3.1 Natural Young’s Modulus of yeast
3.3.2 Sorting by adhesion strength
3.4 Conclusions on the application of an IBM to yeast sorting
4 A deformable cell model for IBM
4.1 Mathematical model of a deformable RBC
4.1.1 Maugis-Dugdale Theory
4.1.2 Generating triangulated meshes of cells
4.1.3 Contact mechanics of a triangulated surface
4.1.4 Elastic model of the cortex
4.1.5 Equation of motion
4.2 Results of the RBC model
4.2.1 Validation of the RBC cortex model
4.2.2 Cell spreading experiments
4.2.3 Visual and static comparison to data
4.2.4 Comparison to dynamic data & influence of parameters
4.2.5 Evolution of forces acting on the cell
4.3 Discussion of the RBC modelling results
4.3.1 Model performance and limitations
4.3.2 Understanding initial cell spreading
4.4 Possible extensions for cells with a more complex cytoskeleton
4.4.1 Random network of actin cortex
4.4.2 Other elements of the cytoskeleton
4.5 Conclusions on the use of the deformable cell model for IBM
5 Software design and computational aspects 1
5.1 Simulation work-flow
5.2 Implementation choices
5.2.1 Key aspects of the software
5.2.2 Documentation and sharing of code
5.3 Modelling techniques currently available
5.3.1 Individual-cell based models
5.3.2 Smoothed particle hydrodynamics
5.3.3 Non-Newtonian smoothed particle hydrodynamics
5.4 Multi-scale methods
5.5 Conclusions on software development
6 Conclusion and future directions
6.1 Development of a flexible software platform for physical simulations
6.2 Experimental protocols to determine the cell mechanical parameters
6.3 Application of IBMs to relevant research problems
6.4 Advancing the state of the art
6.5 Opportunities for future research
A Protocol for Micropipette Aspiration as established in Exeter
A.1 List of materials
A.2 Preparing Micro-Pipettes
A.2.1 Prepare tip
A.2.2 Filling pipettes with buffer
A.3 Preparing Chambers & Cell-suspension
A.4 Pressure System
A.5 Aspiration Setup in Exeter
B Results for AFM measurements on Saccharomyces Cerevisiae
B.1 Protocol for measuring stiffness of yeast with AFM
B.1.1 Materials
B.1.2 Sample preparation
B.1.3 Extracting Young’s modulus from raw data
B.2 Results of stiffness measurements of S. Cerevisiae
B.2.1 Observational errors in the measurements
B.3 Cell-probe protocols
C Brownian motion force for IBM
D Proof that the friction matrix is positive definite
E Rounded triangles: resolution of contact & calculation of contact point
F Bouncing ball simulation and mesh-independence of the contact force
F.1 Meshed bouncing ball
F.2 Meshed sphere adhesion
G Installation of DEMeter
G.1 Prerequisites
G.1.1 System libraries
G.1.2 Environment variables
G.1.3 Boost
G.1.4 CGAL
G.2 Installing DEMeter
G.2.1 Getting DEMeter
G.2.2 Compiling with cmake
Curriculum Vitae
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Biomechanics Section
Division of Mechatronics, Biostatistics and Sensors (MeBioS)

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