Zu den Inhalten springen

4D Imaging / Cardiac NanoDynamics

We use experimental approaches to investigate cardiac ultrastructure on a nano-to-micro scale. Through our research we attempt to elucidate how mechanics (i.e. active such as cell deformation, and passive such as changes in stiffness and ability to bear load) affects electrophysiology and contractile activity of the heart, and vice versa. We are also interested in novel ways the many different cell types present in the heart communicate with one other.

Main research areas are:

1. Organelle deformation during cardiac cycle – structure and functional consequences

The heart is a mechanically-active and -responsive organ, continuously adapting its passive and active mechanical properties in response to changes in demand (for example during exercise, pregnancy, early ‘adaptive’ stages of heart failure) on a beat-by-beat basis as well as with long-lasting remodelling.

One of our main research foci is how intracellular structures inside cardiac muscle cells deform, and how this deformation affects the function of the heart. We specifically investigate the transverse(T)-tubules (TT), sarcoplasmic reticulum, caveolae, mitochondria, and cytoskeleton. We probe the structure (using advanced imaging methods: confocal, multiphoton, and electron microscopy) and function (contractility, ion diffusion) in cells subjected to mechanical manipulations, such as electrical stimulation and stretch of both single cells and multicellular preparations.

A: 3D TT network in a ventricular cardiomyocyte, reconstruction based on confocal microscopy. B: Electron tomography reconstruction, TT (green), sarcoplasmic reticulum (yellow), mitochondria (blue), microtubule (red). C: TT are deformed (squeezed) during stretch and contraction, leading to faster TT content mixing (D).

2. Myocyte-nonmyocyte cross talk in the heart

Many scars – such as in skin – are a-cellular and predominantly composed of fibrillar collagen. In the heart however, fibrotic tissue is very much ‘alive’, with the ubiquitous network of the extracellular matrix (ECM) providing a scaffold for structural and mechanical integration of cells embedded within it. We work to identify novel factors that can influence the bi-directional cross-talk between different cell types. We use a combination of live cell manipulations (genetic, environmental, pharmacological), imaging, and biochemical methods. We use human material provided by the CardioVascular BioBank, to investigate human cardiac diseases such as heart failure and congenital heart defects.

A: Membrane protrusions between a cardiomyocyte and a fibroblast, visualised in vitro using rotating coherent scattering microscopy. B: Electron tomography and reconstruction of cardiomyocyte (CM) and a fibroblast (FB) in infarct border zone.

  • Mechanical deformation of myocyte ultrastructure – structure and function
  • Quantitative T-tubular network analysis
  • Development of novel live fluorescent ion indicators
  • Fibrotic remodelling in Tetralogy of Fallot
  • In vitro fibrosis model