Ine Segers-Nolten

- Short Biography

In 1974 Ine started her HBO education ‘Hoger Natuur Wetenschappelijk Onderwijs (HNWO)’ at the Analistenschool in Groningen. She graduated in 1978 and started working as a biochemical research assistant at the Afdeling Nucleaire Geneeskunde, Academisch Ziekenhuis Groningen on a project concerning hormone dependence of breast tumor development. In 1981 she moved to the University of Twente, Technische Hogeschool Twente at that time, where she was appointed as one of the first members of the starting Biophysical Engineering group headed by Professor Jan Greve. Here she was responsible for setting up a biochemical/cell biological laboratory. She continued working as a research assistant within this group, and participated in many different projects. From 1998 till 2003 she worked as a PhD student within the BPE group on a project using single molecule fluorescence to study the human nucleotide excision DNA repair system. After obtaining her doctoral degree she stayed as a research scientist in the BPE group, later the Nanobiophysics group. Currently she is working part of her time within the NBP alpha-synuclein/ Parkinson’s disease related theme. The other part she spends, as the head of the BioNanoLab facility within the MESA+ institute at the University of Twente.

-Contact Information -

G.M.J.Segers-Nolten (PhD)


University of Twente

Institute for Nanotechnology MESA+

Zuidhorst ZH156

Drienerlolaan 5

7522 NB  Enschede, the Netherlands

PO-box 217

7500AE Enschede, the Netherlands

P +31-(0)53-489-3726

F +31-(0)53-489-1105

-Own Research in NBP-

TOPIC 1: Amyloid as a biomaterial for fabrication of functional nanostructures.

The predominantly neuronal alpha-synuclein protein, implicated in the pathogenesis of Parkinson’s disease and other synucleopathies, self-assembles to form ~10 nm diameter amyloid fibrils that are chemically and mechanically extremely stable. These properties, together with the possibility to site-specifically functionalize the protein, make amyloid an attractive biomaterial for use in the fabrication of nanophotonic and nanoelectronic devices. In contrast to chemical polymer synthesis, amyloid formation is a spontaneous process not requiring addition of catalysts. We aim to create nanophotonic wires by binding specific fluorophores or nanocrystals (quantum dots) to genetically cysteine modified protein molecules constituting the fibrils. Similarly, for use in nanoelectronic devices conductive nanowires will be constructed by attaching nanogold particles to the fibrils.

Current project:

Self-assembled amyloid nanostructures as scaffolds for creating photonic and electronic assemblies (NanoNextNL Programme 7A.4)

TOPIC 2: The role of α-synuclein inclusion bodies in neuronal dysfunction

The presence of Lewy pathology in brain nerve cells is a hallmark of Parkinson’s disease (PD). The Lewy inclusions are largely composed of fibrillar α-synculein protein aggregates (amyloid). The disease is accompanied by nerve cell death and spreading of Lewy pathology over an increasing part of the brain. It is however not clear if nerve cell loss is a direct consequence of the presence of the Lewy pathology. A relation between de number of inclusions in the brain and the severity of the disease has not been found. The formation of inclusions has even been proposed to inhibit or prevent cell degradation. Interestingly, Lewy pathology varies strongly regarding morphology, size and intracellular localization.

In this project we investigate if the spreading of amyloid aggregates and the effect on cell viability depends on the type of protein inclusion present. To this aim we induce α-synculein aggregation in cultured and differentiated SH-SY5Y neuroblastoma cells. After classification of the protein inclusions based on morphology, size, cellular localization and colocalization with other proteins, we determine per category their cytotoxic and infectious properties. Next we will investigate if similar classes of protein aggregates also occur in PD patient brain tissue and if the inclusion type and the disease stage are correlated. To obtain most detailed information we make use of advanced microscopy techniques, like confocal and super-resolution fluorescence microscopy. With this project we hope to gain more insight into the pathogenesis and the mechanism of PD. Possibly the knowledge on inclusion type specific infectious properties enables discrimination and understanding of fast and slowly developing disease types.

Current project:

The role of α-synuclein inclusion bodies in neuronal dysfunction

Researchers: Irene Konings, Kirsten van Leijenhorst-Groener

This project is financially supported by the Stichting Parkinson Fonds, Hoofddorp, The Netherlands.

Other research involvements and interests: fluorescence and atomic force microscopic assessment of amyloid fibril growth and morphology.

Head of the BioNanoLab, MESA+ institute.

Publications of interest


G.M. Segers-Nolten, C. Wyman, N. Wijgers, W. Vermeulen, A.T. Lenferink, J.H. Hoeijmakers, J. Greve and C. Otto, Scanning confocal fluorescence microscopy for single molecule analysis of nucleotide excision repair complexes, Nucleic Acids Res, 30 (2002) 4720-4727


M.E. van Raaij, I.M.J. Segers-Nolten and V. Subramaniam, Quantitative morphological analysis reveals ultrastructural diversity of amyloid fibrils from alpha-synuclein mutants, Biophys J, 91 (2006) L96-98


G.M.J. Segers-Nolten, K.O. van der Werf, M.E. van Raaij and V. Subramaniam, Quantitative characterization of protein nanostructures using atomic force microscopy, Conf Proc IEEE Eng Med Biol Soc, 1 (2007) 6608-6611


M.E. van Raaij, J. van Gestel, I.M.J. Segers-Nolten, S.W. de Leeuw V. and Subramaniam, Concentration dependence of α-synuclein fibril length assessed by quantitative atomic force microscopy and statistical-mechanical theory, Biophys J, 95 (2008) 4871-4878


Y. Roche, D. Zhang, G.M.J. Segers-Nolten, W. Vermeulen, C. Wyman, K. Sugasawa, J. Hoeijmakers and C. Otto, Fluorescence Correlation Spectroscopy of the binding of nucleotide excision repair protein XPC-hHR23B with DNA substrates, J Fluorescence, 18 (2008) 987-995


I. Segers-Nolten, M. Wilhelmus, G. Veldhuis, B. van Rooijen, B. Drukarch and V. Subramaniam, Tissue transglutaminase modulates α-synuclein oligomerization, Protein Science, 17 (2008) 1395-1402


G. Veldhuis, G.M.J. Segers-Nolten, E. Ferlemann and V. Subramaniam, Single molecule FRET reveals structural heterogeneity of SDS-bound α-synuclein, ChemBioChem, 10 (2009) 436-439


K. Volkova, V. Kovalska, G. Segers-Nolten, G. Veldhuis, V. Subramaniam and S. Yarmoluk, S. Explorations of the application of cyanine dyes for quantitative alpha-synuclein detection. Biotech Histochem, 84 (2009) 55-61


H.T. Hoang, I.M. Segers-Nolten, J.W. Berenschot, M.J. de Boer, N.R. Tas, J. Haneveld and M.C. Elwenspoek, Fabrication and interfacing of nanochannel devices for single-molecule studies. J Micromech Microeng, 19 (2009) 065017-065026


K.D. Volkova, V.B. Kovalska, M.Y. Losytskyy, G. Veldhuis, G.M.J. Segers-Nolten, O.I. Tolmachev, V. Subramaniam and S.M. Yarmoluk, Studies of interaction between cyanine dye T-284 and fibrillar alpha-synuclein, J Fluorescence, 20 (2010) 1267-1274


I. Kuperstein, K. Broersen, I. Benilova, J. Rozenski, W. Jonckheere, M. Debulpaep, A. Vandersteen, I. Segers-Nolten, K. Van Der Werf, V. Subramaniam, D. Braeken, G. Callewaert, C. Bartic, R. D'Hooge, I.C. Martins, F. Rousseau, J. Schymkowitz and B. De Strooper, Neurotoxicity of Alzheimer's disease Abeta peptides is induced by small changes in the Abeta(42) to Abeta(40) ratio, EMBO J, 29 (2010) 3408-3420


H.T. Hoang, I.M. Segers-Nolten, N.R. Tas, J.W. van Honschoten, V. Subramaniam and M.C. Elwenspoek, Analysis of single quantum-dot mobility inside 1D nanochannel devices, Nanotechnology, 22 (2011) 275201-275209


I.B. Bruinsma, K.A. Bruggink, K. Kinast, A.A.M. Versleijen, I.M.J. Segers-Nolten, V. Subramaniam, H.B. Kuiperij, W. Boelens, R.M.W. de Waal, and M.M. Verbeek, Inhibition of alpha-synuclein aggregation by small heat shock proteins. Proteins, 79 (2011) 2956-2967


H.T. Hoang, H.D. Tong, I.M. Segers-Nolten, N.R. Tas, V. Subramaniam, and M.C. Elwenspoek, Wafer-scale thin encapsulated two-dimensional nanochannels and its application toward visualization of single molecules. J. Colloid & Interface Sci., 367 (2012), 455-459


K.K.M. Sweers, I.M.J. Segers-Nolten, M.L. Bennink, and V. Subramaniam, Structural model for alpha-synuclein fibrils derived from high resolution imaging and nanomechanical studies using atomic force microscopy. Soft Matter, 8 (2012) 7215-7222


N. Zijlstra, C. Blum, I.M.J. Segers-Nolten, M.M.A.E. Claessens, and V. Subramaniam, Molecular composition of sub-stoichiometrically labeled a-synuclein oligomers determined by single-molecule photobleaching. Angewandte Chemie, Int. Ed. Engl., 51 (2012) 8821-8824


V.B. Kovalska, M. Yu Losytskyy, O.I. Tolmachev, Y.L. Slominskii, G.M.J. Segers-Nolten, V. Subramaniam, and S.M. Yarmoluk, Tri- and pentamethine cyanine dyes for fluorescent detection of alpha-synuclein oligomeric aggregates. J. Fluorescence, 22 (2012) 1441-1448


A. Sidhu, I. Segers-Nolten, and V. Subramaniam, Solution conditions define morphological homogeneity of alpha-synuclein fibrils. BBA proteins and Proteomics, 1844 (2014) 2127-2134


M.H. Shabestari, P. Kumar, I.M.J. Segers-Nolten, M.M.A.E. Claessens, B.D. van Rooijen, V. Subramaniam, and Huber, M. Three long-range distance constraints and an approach towards a model for the alpha-synuclein fibril fold. Appl. Magn. Res., (2015) DOI 10.1007/s00723-014-0622-7

Book contribution:


I. Segers-Nolten, M. van Raaij, and V. Subramaniam, (2011) Biophysical Analysis of Amyloid Formation. Comprehensive Biomaterials, Eds. Ducheyne, P., Healy, K., Hutmacher , D.W., Grainger, D.W. and Kirkpatrick, C.J. Elsevier Ltd., Volume 2, 347-359