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Development of advanced optical tools for studying cellular mechanics at high spatial and temporal resolution

Project description

Novel optical imaging tools to study live tissue

In the life sciences, non-invasively assessing the mechanical properties of living cells with a spatio-temporal resolution similar to that of fluorescence microscopy remains a challenge. Despite its ability to probe the viscoelastic properties of materials with diffraction-limited resolution in 3D, the recently developed type of optical elastography called Brillouin microscopy (BM) has very low speed, high phototoxicity and difficulties in quantification. Seeking to overcome these drawbacks, the EU-funded Brillouin4Life project will develop unique and innovative optical imaging technologies based on BM. These novel technologies will maximise speed, resolution and depth penetration, while minimising photodamage. The project will establish BM as a revolutionary tool for live tissue and cellular biophysics studies.

Objective

A long-standing aim in the life sciences is to understand development and morphogenesis, i.e. how organismal shape is encoded by the genome and how cellular mechanics are involved in its execution. Lately, investigations have started to focus on the mechanical properties of the involved multicellular compartments, and the interwoven mechanical - molecular interactions at the cellular scale. While molecular components can routinely be visualized with fluorescence microscopy, assessing the mechanical properties of living cells with similar spatio-temporal resolution in a non-invasive fashion has long been an open challenge.

Recently, a new type of optical elastography, namely Brillouin microscopy (BM), has emerged as a non-destructive, label- and contact-free technique which can probe visco-elastic properties of materials with diffraction-limited resolution in 3D. Yet, despite ongoing improvements, virtually all current implementations suffer from very low speed, high phototoxicity, and difficulties in quantification, thus prohibiting meaningful investigations in the life sciences.

In this interdisciplinary proposal, my group will develop unique and innovative optical imaging technologies based on BM to overcome its current drawbacks and to establish it as a revolutionary tool for live tissue and cellular biophysics studies. In particular, we will work towards a highly-multiplexed BM with selective-plane illumination to maximize speed, resolution and depth penetration, while minimizing photodamage (Aim 1). At the same time, we will combine BM with other imaging modalities that will allow us to obtain correlative datasets and to accurately quantify the measured mechanical properties (Aim 2). We will then apply these methodological advancements together with fellow biologists to study the role of elasticity in tissue morphogenesis and self-organisation, thereby contributing to a better understanding of the role of biomechanics in developmental biology (Aim 3).

Host institution

EUROPEAN MOLECULAR BIOLOGY LABORATORY
Net EU contribution
€ 1 999 289,00
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
Links
Total cost
€ 1 999 289,00

Beneficiaries (1)