Thesis subject
BSc & MSc - Molecular modeling of biomembranes
Biomembranes are key structural and functional elements of all biological cells. To understand how the lipid matrix supports various membrane proteins and vice versa is one of the largest scientific challenges of this century.
The number of solved structures (X-ray crystallography) for membrane proteins is still embarrassing low, let alone that we understand how these proteins do their thing or how the lipids integrate proteins in a bilayer topology. There is a big need for methods that can help us to understand more of these and other important issues.
![A Singer-Nicholson model of a membranestructure containing membrane proteins [Engelman, Nature 2005] A Singer-Nicholson model of a membranestructure containing membrane proteins [Engelman, Nature 2005]](/upload_mm/a/f/b/91881d95-528a-4c99-bdc4-9d5c0d69c799_franssingernicholson1_670x243.jpg)
At PCC we try to model various aspects of biomembranes using tools borrowed from various disciplines and combine this in a self-consistent field (SCF) theory. We use the Van der Waals theory for the demixing of oil and water to account for the driving force for membrane formation, leading to dense packings of lipid tails. The Poisson Boltzmann theory is used to account for the charges in the lipid heads and the hydrated parts of the proteins (unstructured tails). The theory of Scheutjens and Fleer helps us to account for conformational degrees of freedom of lipids and conformationally disordered parts of the proteins. Using these and other tools developed to understand soft matter systems, we try to answer how, e.g., a size mismatch between lipids and proteins induce protein segregation, how a non-trivial shape of proteins can induce membrane curvature, etcetera.
In a recent paper of Kik et al. [1] we forwarded a simple model for trans-membrane proteins and how a hydrophobic mismatch perturbs the lipids layers in its vicinity. The proteins were modeled as a cylindrical inclusion without molecular details. Our interest was to unravel how lipids mediate the interactions between such ‘toy’ inclusions. To keep computation times in bounds the geometry of interacting objects was compromised. New developments in numerical algorithms to solve the SCF equations and increasing computer power enables us now to design more realistic models and answer new questions.
There are many research targets and an incomplete list may include:
- Design and analyze various models for trans-membrane proteins and study the colloidal stability (BSc and MSc)
- Study asymmetric membranes (MSc)
- Study scenarios of how particles or large molecules can cross a membrane (MSc)
- Inhomogeneous distribution of lipids and membrane proteins in so-called Rafts (BSc and MSc)
- Membrane-membrane interactions induced by membrane bound proteins (BSc and MSc)
- Supported membranes, adsorbed vesicles (BSc and MSc)
- Membranes in concentration gradients (steady states) (MSc)
We are keen to study problems for which experimental data is available, but we are not limited to this. Invariably you will need to study a large number of theoretical aspects (basically because membrane problems have many different aspects). This will not only help you to understand what your modeling results are telling you, but it will also increase your overall insight in the behavior of soft matter in general.
Techniques:
There are not many constraints to join our project.
- Quite essential is that you have a strong interest in biomembranes and know, or are keen to know, much about the topic. This means that you study the relevant literature in search for potential modeling opportunities or to find a match between theory and experiment (more difficult for simplistic models than for molecularly detailed ones).
- It is true that the work heavily makes use of PC/workstations, but you do not need to be an expert in computers to join the team. When you happen to have experience in c++ programming you may get involved in the ‘kitchen’ of SCF modeling, but you can contribute without going in these details. Data-analysis and visualization is a typical activity/research challenge.
References:
1. R.A. Kik, F.A.M. Leermakers, J.M. Kleijn "Molecular modeling of proteinlike inclusions in lipid bilayers: Lipid-mediated interactions." Phys. Rev. E81 (2010) 021915.