Research

Cell micromechanics

Bruising of plant cells

Smoothed Particle Hydrodynamics (SPH) is a computational method that discretizes a set of partial differential equations (PDEs) by attributing the local density to distinct particles using a smoothing kernel. The advantage of SPH compared to conventional discretization methods such as the finite element method is that it handles large deformations more easily. Specifically, simulating damage of the components, such as fracture or bruising, becomes possible, which proves useful in modeling material failure.

SPH can be used to model the dynamics of compression or impact on plant cells. The intracellular fluid and the cell wall are represented by distinct particles with the appropriate visco-elastic behavior. Using multi-scale methods, the model can be scaled up for dealing with a large number of cells.

Mechanics of cell aggregates

To gain deeper understanding of the properties of biological systems  such as cell colonies and tissues, modeling techniques are of utmost importance. The strong development of physical biology in general in the last decade supports this point of view. An individual cell based, mesh-free modeling technique ensures physically meaningful, directly measurable model parameters. The particle-based software DEMeter++ is being used as a powerful platform for simulations.

Yeast colony formation

To show the validity of the modeling approach and address our most fundamental questions (see below), it is essential to model relatively simple and biologically well understood systems. Yeast (S. cerevisiae) colonies certainly qualify as such a system, and already pose very interesting and demanding problems.

The most fundamental question we hope to address with this research is wide open for almost all imaginable systems today: How much and in what ways is the colony/biofilm/tissue of the biological system in question influenced or even determined by pure (cell) mechanics? In the case of yeast colonies, the most interesting biological questions which we want to address is: How do adhesion properties lead to cell sorting and to evolutionary stable proportions of adhering and non-adhering cells? How do yeast colonies wrinkle?

Mechanical microenvironment in 3D cell cultures

A second system we are aiming for with direct medical impact are chondroprogenitors which differentiate to form bone tissue. In bone tissue engineering, in vitro bioartificial tissue is grown for use in transplantation in large and non-healing bone defects. The first step is achieving cell growth in three dimensions.The biophysical microenvironment to which cells are exposed during in vitro growth, strongly affects their in vitro growth potential on the one hand and their in vivo potential to regenerate tissues on the other hand.

Moreover, process design variables influence the in vitro microenvironment, so that quantification of the relation in between there is essential for an effective process design. We combine individual-based modelling techniques with in vitro measurements, to investigate how process design influences the microenvironment. The research focuses on two stages of cell and tissue growth that are essential to many tissue engineering and cellular therapies: the expansion phase and the aggregation phase. The individual-based model simulates the mechanics and mass transport of cells and microcarriers in a rotation bioreactor. Single-cell mechanical measurements and experimental cell cultures are being performed to train and validate the model.