The importance of mechanics in biological design can be seen all around us, from spider webs to the musculoskeletal system. This relationship extends to the microscopic world and our lab investigates how mechanics control biological functioning on small length-scales, ranging from protein shells to multicellular assemblies.
To understand the steps that lead to viral infection, we study the mechanical properties of virus capsids at different stages of their life cycle. It is now well established that viruses are very robust when they travel between host organisms but we showed how mechanical changes of their protein shell eventually allow them to open up to release their genetic material1. In the case of influenza virus, we discovered that sequential uncoating steps are required to achieve maximal infectivity2. Along similar lines, we aim to understand the mechanical contribution of clathrin protein lattices to the formation of membrane vesicles in cells, an essential process in endocytosis and intracellular transport.
The lessons that we learn from studying the mechanical architecture of such biological complexes can also be exploited to improve their application in nanotechnology. For example, clathrin proteins, normally involved in the formation of transport vesicles in cells, can be applied to form very regular and stable lattices on almost any type of surface3. This surface functionalization could be a first step to fabricate more efficient sensors or biosynthetic reactors.
To measure the mechanical response, we indent or stretch our samples on a sub-micrometer length-scale using atomic force microcopy, optical trapping, and standing acoustic waves4. Because we perform our experiments in a controlled liquid environment, we can mimic events that are triggered by temperature, chemicals, pH, or force. Finite element analysis is employed to model the experiments in order to extract the relevant mechanical parameters.
Most of our research projects are carried out as national or international collaborations, in which we provide the nano-mechanical expertise while our partners are experts on the specific biological system5.
Selected publications:
(1) A. Ortega-Esteban, K. Bodensiek, C. San Martín, M. Suomalainen, U.F. Greber, P.J. de Pablo, I.A.T. Schaap (2015) Fluorescence tracking of genome release during the mechanical unpacking of single viruses. ACS Nano. 9, 10571-10579.
(2) S. Li, C. Sieben, K. Ludwig, C.T. Höfer, S. Chiantia, A. Herrmann, F. Eghiaian, I.A.T. Schaap (2014) pH-controlled two-step uncoating of influenza virus. Biophys. J. 106, 1447-1456.
(3) P.N. Dannhauser, M. Platen, H. Böning, I.A.T. Schaap (2015) Durable protein lattices of clathrin that can be functionalized with nano-particles and active bio-molecules. Nat. Nanotechnol. 10, 954-957.
(4) A. Lamprecht, S. Lakämper, T. Baasch, I.A.T. Schaap, J. Dual (2016) Imaging the position-dependent 3D force on microbeads subjected to acoustic radiation forces and streaming. Lab Chip. 16, 2682-2693.
(5) S. Nawaz, P. Sánchez, S. Schmitt, N. Snaidero, M. Mitkovski, C. Velte, B.R. Brückner, T. Czopka, S. Jung, J.S. Rhee. A. Janshoff, W. Witke, I.A.T. Schaap, D. Lyons, M. Simons (2015) Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system. Dev. Cell. 34, 139-151
We are part of the Institute of Biological Chemistry, Biophysics and Bioengineering (IB3) at the Heriot Watt University in Edinburgh, UK.
We
acknowledge support from the Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)
Cluster of Excellence 171, the SFB 860, and the Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences (GGNB).
Cluster of Excellence 171, the SFB 860, and the Göttingen Graduate School for Neurosciences, Biophysics, and Molecular Biosciences (GGNB).
Dr. Iwan A.T. Schaap
tel: +44 131 451 4145
i.schaap (at) hw.ac.uk
Institute of Biological Chemistry, Biophysics and Bioengineering
School of Engineering and Physical Sciences
Heriot-Watt University
EH14 4AS Edinburgh, UK