Dr Pavel Novak
Lecturer in Biomedical Engineering and Biomaterials
One of the biggest challenges in molecular cell biology is to understand how the molecular machines that make up a living cell are organized in 3D space and how they interact together on a nanometre scale under physiological conditions. At the same time, biomedical applications of nano-engineered materials often face a challenge closely related to the one mentioned above - that is how to manipulate, modify or even create nano-sized structures right at the biointerface under physiological conditions. Out of all the different approaches to this problem that have emerged over the last few decades, the family of scanning probe microscopy (SPM) appears to be one of the most promising thanks to the fact that the imaging probe doubles as a nano-manipulation tool. We work on combining principles of scanning probe microscopy, electrochemistry, biophysics, molecular biology, neuroscience, and bioengineering to visualize, quantify, and manipulate live cellular processes and nano-engineered structures at nanoscale. The technique is ideally suited to non-contact probing the electrophysiology of cilia with a nanometer resolution and can also be used to provide simultaneous physical or chemical stimuli direct to the cilium.
This multidisciplinary effort, bringing together research teams from Queen Mary, Imperial College London, Cambridge University, and University College London will facilitate formulation of 3D quantitative models of sub-cellular structures and molecular complexes and provide novel tools for nanomedicine and nanoengineering.
Kong D, Peng L, Di Cio S, Novak P and Gautrot JE (2018). Stem Cell Expansion and Fate Decision on Liquid Substrates Are Regulated by Self-Assembled Nanosheets. Acs Nano vol. 12, (9) 9206-9213. 10.1021/acsnano.8b03865
Zhou Y, Saito M, Miyamoto T, Novak P, Shevchuk AI, Korchev YE, Fukuma T and Takahashi Y (2018). Nanoscale Imaging of Primary Cilia with Scanning Ion Conductance Microscopy. Anal Chem vol. 90, (4) 2891-2895. 10.1021/acs.analchem.7b05112
Thompson CL, Plant JC, Wann AK, Bishop CL, Novak P, Mitchison HM, Beales PL, Chapple JP and Knight MM (2017). Chondrocyte expansion is associated with loss of primary cilia and disrupted hedgehog signalling. Eur Cell Mater vol. 34, 128-141. 10.22203/eCM.v034a09
Vivekananda U, Novak P, Bello OD, Korchev YE, Krishnakumar SS, Volynski KE and Kullmann DM (2017). Kv1.1 channelopathy abolishes presynaptic spike width modulation by subthreshold somatic depolarization. Proc Natl Acad Sci U S A vol. 114, (9) 2395-2400. 10.1073/pnas.1608763114
Clarke RW, Novak P, Zhukov A, Tyler EJ, Cano-Jaimez M, Drews A, Richards O, Volynski K, Bishop C and Klenerman D (2016). Low Stress Ion Conductance Microscopy of Sub-Cellular Stiffness. Royal Society of Chemistry Soft Matter vol. 12, (38) 7953-7958. 10.1039/c6sm01106c
Zhang Y, Clausmeyer J, Babakinejad B, Córdoba AL, Ali T, Shevchuk A, Takahashi Y, Novak P, Edwards C, Lab M, Gopal S, Chiappini C, Anand U, Magnani L, Coombes RC, Gorelik J, Matsue T, Schuhmann W, Klenerman D, Sviderskaya EV and Korchev Y (2016). Spearhead Nanometric Field-Effect Transistor Sensors for Single-Cell Analysis. Acs Nano vol. 10, (3) 3214-3221. 10.1021/acsnano.5b05211
Miragoli M, Sanchez-Alonso JL, Bhargava A, Wright PT, Sikkel M, Schobesberger S, Diakonov I, Novak P, Castaldi A, Cattaneo P, Lyon AR, Lab MJ and Gorelik J (2016). Microtubule-Dependent Mitochondria Alignment Regulates Calcium Release in Response to Nanomechanical Stimulus in Heart Myocytes. Cell Rep vol. 14, (1) 140-151. 10.1016/j.celrep.2015.12.014
Seifert J, Rheinlaender J, Novak P, Korchev YE and Schaeffer TE (2015). Comparison of atomic force microscopy and scanning ion conductance microscopy for live cell imaging. European Biophysics Journal With Biophysics Letters vol. 44, S83-S83.
Seifert J, Rheinlaender J, Novak P, Korchev YE and Schäffer TE (2015). Comparison of Atomic Force Microscopy and Scanning Ion Conductance Microscopy for Live Cell Imaging. Langmuir vol. 31, (24) 6807-6813. 10.1021/acs.langmuir.5b01124
Novak P, Shevchuk A, Ruenraroengsak P, Miragoli M, Thorley AJ, Klenerman D, Lab MJ, Tetley TD, Gorelik J and Korchev YE (2014). Imaging single nanoparticle interactions with human lung cells using fast ion conductance microscopy. Nano Letters vol. 14, (3) 1202-1207. 10.1021/nl404068p
Actis P, Tokar S, Clausmeyer J, Babakinejad B, Mikhaleva S, Cornut R, Takahashi Y, López Córdoba A, Novak P, Shevchuck AI, Dougan JA, Kazarian SG, Gorelkin PV, Erofeev AS, Yaminsky IV, Unwin PR, Schuhmann W, Klenerman D, Rusakov DA, Sviderskaya EV and Korchev YE (2014). Electrochemical nanoprobes for single-cell analysis. Acs Nano vol. 8, (1) 875-884. 10.1021/nn405612q
Babakinejad B, Jönsson P, López Córdoba A, Actis P, Novak P, Takahashi Y, Shevchuk A, Anand U, Anand P, Drews A, Ferrer-Montiel A, Klenerman D and Korchev YE (2013). Local delivery of molecules from a nanopipette for quantitative receptor mapping on live cells. Anal Chem vol. 85, (19) 9333-9342. 10.1021/ac4021769
Novak P, Gorelik J, Vivekananda U, Shevchuk AI, Ermolyuk YS, Bailey RJ, Bushby AJ, Moss GWJ, Rusakov DA, Klenerman D, Kullmann DM, Volynski KE and Korchev YE (2013). Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels. Neuron vol. 79, (6) 1067-1077. 10.1016/j.neuron.2013.07.012
Shevchuk AI, Novak P, Velazquez MA, Fleming TP and Korchev YE (2013). Combined ion conductance and fluorescence confocal microscopy for biological cell membrane transport studies. Journal of Optics (United Kingdom) vol. 15, (9) 10.1088/2040-8978/15/9/094005
Miragoli M, Novak P, Ruenraroengsak P, Shevchuk AI, Korchev YE, Lab MJ, Tetley TD and Gorelik J (2013). Functional interaction between charged nanoparticles and cardiac tissue: a new paradigm for cardiac arrhythmia? Nanomedicine (Lond) vol. 8, (5) 725-737. 10.2217/nnm.12.125
Bhargava A, Lin X, Novak P, Mehta K, Korchev Y, Delmar M and Gorelik J (2013). Super-resolution scanning patch clamp reveals clustering of functional ion channels in adult ventricular myocyte. Circ Res vol. 112, (8) 1112-1120. 10.1161/CIRCRESAHA.111.300445
Klenerman D, Shevchuk A, Novak P, Korchev YE and Davis SJ (2013). Imaging the cell surface and its organization down to the level of single molecules. Philosophical Transactions of The Royal Society B: Biological Sciences vol. 368, (1611) 10.1098/rstb.2012.0027
Shevchuk AI, Novak P, Taylor M, Diakonov IA, Ziyadeh-Isleem A, Bitoun M, Guicheney P, Lab MJ, Gorelik J, Merrifield CJ, Klenerman D and Korchev YE (2012). An alternative mechanism of clathrin-coated pit closure revealed by ion conductance microscopy. Rockefeller University Press. Journal of Cell Biology vol. 197, (4) 499-508. 10.1083/jcb.201109130
Takahashi Y, Shevchuk AI, Novak P, Babakinejad B, Macpherson J, Unwin PR, Shiku H, Gorelik J, Klenerman D, Korchev YE and Matsue T (2012). Topographical and electrochemical nanoscale imaging of living cells using voltage-switching mode scanning electrochemical microscopy. Proceedings of The National Academy of Sciences Proceedings of The National Academy of Sciences of The United States of America vol. 109, (29) 11540-11545. 10.1073/pnas.1203570109
Ruenraroengsak P, Novak P, Berhanu D, Thorley AJ, Valsami-Jones E, Gorelik J, Korchev YE and Tetley TD (2012). Respiratory epithelial cytotoxicity and membrane damage (holes) caused by amine-modified nanoparticles. Informa Healthcare Nanotoxicology vol. 6, (1) 94-108. 10.3109/17435390.2011.558643
Takahashi Y, Shevchuk AI, Novak P, Zhang Y, Ebejer N, MacPherson JV, Unwin PR, Pollard AJ, Roy D, Clifford CA, Shiku H, Matsue T, Klenerman D and Korchev YE (2011). Multifunctional nanoprobes for nanoscale chemical imaging and localized chemical delivery at surfaces and interfaces. Angewandte Chemie - International Edition vol. 50, (41) 9638-9642. 10.1002/anie.201102796
Shevchuk AI, Novak P, Takahashi Y, Clarke R, Miragoli M, Babakinejad B, Gorelik J, Korchev YE and Klenerman D (2011). Realizing the biological and biomedical potential of nanoscale imaging using a pipette probe. Nanomedicine vol. 6, 565-575. 10.2217/NNM.10.154
Miragoli M, Moshkov A, Novak P, Shevchuk A, Nikolaev VO, El-Hamamsy I, Potter CMF, Wright P, Kadir SHSA, Lyon AR, Mitchell JA, Chester AH, Klenerman D, Lab MJ, Korchev YE, Harding SE and Gorelik J (2011). Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cells. Journal of The Royal Society Interface vol. 8, 913-925. 10.1098/rsif.2010.0597
Foeldes G, Mioulane M, Wright JS, Liu AQ, Novak P, Merkely B, Gorelik J, Schneider MD, Ali NN and Harding SE (2011). Modulation of human embryonic stem cell-derived cardiomyocyte growth: A testbed for studying human cardiac hypertrophy? Journal of Molecular and Cellular Cardiology vol. 50, 367-375. 10.1016/j.yjmcc.2010.10.029
Takahashi Y, Shevchuk AI, Novak P, Murakami Y, Shiku H, Korchev YE and Matsue T (2010). Simultaneous noncontact topography and electrochemical imaging by SECM/SICM featuring ion current feedback regulation. Journal of The American Chemical Society vol. 132, (29) 10118-10126. 10.1021/ja1029478
Nikolaev VO, Moshkov A, Lyon AR, Miragoli M, Novak P, Paur H, Lohse MJ, Korchev YE, Harding SE and Gorelik J (2010). ?
Adler J, Shevchuk AI, Novak P, Korchev YE and Parmryd I (2010). Plasma membrane topography and interpretation of single-particle tracks. Nature Methods vol. 7, 170-171. 10.1038/nmeth0310-170
Richards O, Johson N, Li C, Novak P, Clarke R, Korchev Y and Klenerman D (2010). Probing the Interaction between a Nanopipette and a Soft Surface Using Scanning Ion Conductance Microscopy (SICM). Biophysical Journal vol. 98, (3) 394A-394A.
Burkinshaw L, Clarke R, Novak P, Korchev Y and Klenerman D (2010). Surface Charge Mapping Based on Scanning Ion Conductance Microscopy. Biophysical Journal vol. 98, (3) 394A-394A.
Novak P, Li C, Shevchuk AI, Stepanyan R, Caldwell M, Hughes S, Smart TG, Gorelik J, Ostanin VP, Lab MJ, Moss GWJ, Frolenkov GI, Klenerman D and Korchev YE (2009). Nanoscale live-cell imaging using hopping probe ion conductance microscopy. Nature Methods vol. 6, (4) 279-281. 10.1038/nmeth.1306
Sanchez D, Johnson N, Li C, Novak P, Rheinlaender J, Zhang Y, Anand U, Anand P, Gorelik J, Frolenkov GI, Benham C, Lab M, Ostanin VP, Schaeffer TE, Klenerman D and Korchev YE (2008). Noncontact measurement of the local mechanical properties of living cells using pressure applied via a pipette. Biophysical Journal vol. 95, (6) 3017-3027. 10.1529/biophysj.108.129551
Novak P, Gaburjakova M and Zahradnik I (2007). BLM Analyzer: a software tool for experiments on planar lipid bilayers. Biotechniques vol. 42, 335-+. 10.2144/000112384
Novak P and Zahradnik I (2006). Q-method for high-resolution, whole-cell patch-clamp impedance measurements using square wave stimulation. Annals of Biomedical Engineering vol. 34, 1201-1212. 10.1007/s10439-006-9140-6
Novak P and Zahradnik I (2005). Computer-aided formation of the whole-cell patch-clamp recording configuration. General Physiology and Biophysics vol. 24, 337-348.