From single cells to emergent mechanical properties of tissue
Find out more about subscribing to add all events.
From single cells to emergent mechanical properties of tissue
Wed, 17/06/2020 - 13:30 to 14:30
Speaker:
Oliver Otto
Affiliation:
University of Greifswald, Germany
Synopsis:
The mechanical properties of cells have long been established as a sensitive and label-free biomarker for cell and tissue function. While mechanical cell assays have traditionally been limited to low throughput or small sample size, our development of real-time deformability
1,2
cytometry increased analysis rates to up to 1,000 cells per second
discuss how this breakthrough technology provided a new perspective on life science research by enabling the first time a high-throughput mechanical characterisation of heterogeneous biological samples on a single cell level. This includes monitoring the invasion of the Malaria parasite into erythrocytes, studying the impact of magnetic nanoparticles on blood platelets,
3-5
and to assess the quality of manufactured red blood cells
.
The second part of my presentation focuses on multicellular structures and the question how mechanical properties of cells contribute to tissue rheology. Until recently, a high-throughput technology for mechanical characterisation of tissue had been elusive. We answered this
6
challenge by introducing virtual fluidic channels . Virtual channels are liquid-bound
microfluidic constrictions of variable cross-sections, which can be modified within seconds and tailored to hydrodynamic stress distributions to match a wide size range of biological samples. We perform high-throughput rheology on spheroids as a 3D tissue model system and demonstrate that the Young’s modulus of isolated cells exceeds the one of tissue by one order of magnitude. Interestingly, our results suggest that tissue elasticity is mainly driven by cell- cell interactions and extracellular matrix contributions.
References:
1. O. Otto, P. Rosendahl, A. Mietke, S. Golfier, C. Herold, D. Klaue, S. Girardo, S. Pagliara,
A. Ekpenyong, A. Jacobi, M. Wobus, N. Töpfner, U.F. Keyser, J. Mansfeld, E. Fischer-Friedrich, and J. Guck Real-time deformability cytometry: on-the-fly cell mechanical phenotyping
Nature Methods 12, 199-202 (2015)
2. B. Fregin, F. Czwerwinski, D. Biedenweg, Girardo, S., Gross S., K. Aurich, and O. Otto
Dynamic real-time deformability cytometry: high-throughput single-cell rheology in complex samples Nature Communications 10, 415 (2019)
3. M. Koch, K.E. Wright, O. Otto, M. Herbig, N.D. Salinas, N.H. Tolia, T.J. Satchwell, J. Guck, N.J. Brooks, and J. Baum
Plasmodium falciparum erythrocyte-binding antigen 175 triggers a biophysical change in the red blood cell that facilitates invasion
PNAS 114, 201602843 (2017)
4. K. Aurich, B. Fregin, R. Palankar, J. Wesche, O. Hartwich, D. Biedenweg, TH. Nguyen, A. Greinacher, and O. Otto
Label-free on chip quality assessment of cellular blood products using real-time deformability cytometry Lab on a Chip (accepted for publication)
5. E. Guzniczak, O. Otto, G. Whyte, N. Willoughby, M. Jiminez, and H. Bridle Deformability-induced lift force in spiral microchannels for cell separation Lab on a Chip 10.1039/c9lc01000a (2020)
6. M.H. Panhwar, F. Czerwinski, V.A.S. Dabbiru, Y. Komaragiri, B. Fregin, D. Biedenweg, P. Nestler, R.H. Pires, and O. Otto
High-throughput cell and spheroid mechanics in virtual fluidic channels Nature Communications 11, 2190 (2020)
Biography:
The research group of Oliver Otto focuses on understanding how mechanical properties of molecules, cells and tissue impact on biological function. Specifically, he is interested in the development of novel optical methods, microfluidic systems and synthetic tissue models to study the rheology of single cells and multicellular systems at high spatiotemporal resolution.
Oliver received his PhD in Physics from the University of Cambridge (UK) where he investigated single molecule dynamics at the Cavendish Laboratory under the supervision of Prof. Ulrich Keyser. In 2012, he joined the Technical University of Dresden (Germany) as a postdoctoral researcher in the group of Prof. Jochen Guck where he was working on the translation of high-throughput screening into the field of cell mechanics. His newly developed method – Real-Time Deformability Cytometry – allowed for the first time the measurement of cell mechanical properties with the throughput of a flow cytometer. Since 2016 Oliver is an independent group leader at the Centre for Innovation Competence – Humoral Immune Reactions in Cardiovascular Disorders at the University of Greifswald (Germany). He leads a group of ten interdisciplinary researchers combining expertise in Biology, Engineering as well as Physics.
Oliver Otto published more than 40 peer-reviewed manuscripts, including high-impact journals (Nature Methods, Nature Communications) and supervises an increasing number of young researches at the Bachelor, Master as well as PhD level. As a co-founder of the spin-off company “Zellmechanik Dresden GmbH” where he currently holds the position as a Chief Scientific Officer, Oliver is also dedicated to the translation of scientific results into business strategies.