Research Groups

ALF HONIGMANN
GROUP

Membrane Biophysics of Cells and Tissues

Biological membranes are fascinating composites of lipids, proteins and sugars. Our aim is to understand how the molecular components self-organize into meso-scale complexes that control processes as adhesion, polarization, signaling / sensing, which underlie morphogenesis of cells and tissues.

To this end, we pursue a mutli-scale approach:

(1) Supra-Molecular-Organization of Membrane Complexes in Cells and Tissues 
We use and develop super-resolution STED microscopy in combination with 3D tissue culture to study how molecules organize into functional meso-scale structures. Currently we are working on the Apical Junction Complex. 

(2) Reconstitution of Membrane Complexes by Molecular Self-Organization in vitro 
We purify key organizing proteins to re-assemble complex structures and functions in controlled in vitro membrane systems. We are particularly interested in collective processes such as phase transitions / separation and active feedback systems.

(3) Control of Morphogenesis in Epithelial Organoids
We aim to apply and test the molecular and mesoscale self-organization principles during the morphogenesis of stem cell derived organoids. We especially focus on the interplay of cell adhesion, cortical mechanics and cell differentiation.

 

 

Projects:

Riccardo Maraspini

Supramolecular Architecture of the Apical-Junctional-Complex

We combine 3D super-resolution STED microscopy with 3D cell culture to reconstruct the structure of the apical-junctional complex of mammalian epithelial cells. Based on STED imaging of ~20 different junctional proteins we are assembling a supra-molecular model of the APJ. Our model reveals and quantifies stratification of receptors, adapters, scaffolders and cell cortex components from the membrane towards the cytoplasm as well as the asymmetric distribution of polarity proteins along the apical basal axis. This work provides the structural basis to understand assembly of the junctional ring, its mechanical properties and its role in signalling and polarity.  

 

Phase Separation of Lipids - Proteins & Compartmetalization

Simple lipid mixtures on its own already show fascinating self-organization behavior (phase separation, curvature, budding and fusion). However, in biological membranes regulation of structure and function arises from the interplay of proteins with lipids. The crux is these lipid-protein interactions are generally weak and transient which makes it very challenging to study. Even though transient and weak it is becoming more and more obvious that lipid protein interactions are the key for many regulatory processes in which specific protein complexes have to be formed for example upon stimuli during cell signaling. It is suspected that the composition of bio-membranes is specifically tuned to respond on these small stimuli with a local self-reorganization which induces and amplifies the (protein) function. Our goal is to understand the mechanisms which drive local self-reorganization in the membrane. We showed that pinning of membrane lipids and proteins by the cell cortex can induce local membrane reorganization dependent on the affinity of the pinning species.

Methodological and technical expertise

  • Super-Resolution Microscopy (STED, SMLM)
  • Fluorescence Correlation Spectroscopy, Single Molecule Tracking
  • Membrane labelling (lipids and proteins) in vivo and in vitro
  • Micro-Patterning of Surfaces for  Control of Cell Attachment, Signaling and Differentiation
  • Reconstitution of Membrane Proteins in Model Membranes