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Sara Snogerup Linse


Department of Biochemistry and Structural Biology

Phone: +46 46 222 8246
Fax: +46 46 222 4116


Research Group 

Tommy Cedervall, Scientist 
Risto Cukalevski, PhD Student  
Birgitta Frohm, Research Engineer
Ricardo Gaspar, PhD Student 
Stefan Gunnarsson, PhD Student
Thom Leiding, Scientist  
Karin Mattsson, PhD Student 
Kalyani Sanagavarapu, PhD Student
Elodie Sanfins, Postdoc
Tanja Weiffert, PhD Student 
Xiaoting Yang, PhD Student

Research Interests

Calcium signaling networks

The calcium ion is a ubiquitous second messenger involved in the regulation of a vast number of cellular and extracellular activities in the body, including memory and learning. We investigate the interactions of calcium signaling proteins with target proteins and metal ions. We identify novel targets and quantify their binding parameters and functional effects. Particular emphasis is on calmodulin and the two hexa-EF-hand proteins secretagogin and calbindin D28k. We have recently discovered a large set of novel targets of human calmodulin, and of particular interest is the finding of a large number of transmembrane proteins. For secretagogin we have discovered a number of vesicle-associated target proteins, and for calbindin an enzyme involved in phospho-inositol singalling.

Link to CaLigator software

Protein amyloid formation 

Several proteins have been found in large aggregates, amyloid, with highly similar cross beta structure. The aggregating segment is often part of a larger peptide of protein with rather wide tolerance for amino acid sequence and native structure. We investigate the aggregation process and the influence of intrinsic (sequence) and extrinsic (solution conditions, lipid membranes, additives, other proteins, etc.) factors. We have developed highly efficient expression and purification systems for several amyloid proteins, including amyloid beta peptide from Alzheimer’s disease. We have achieved unforeseen reproducibility of kinetic assays and found that amyloid formation follows the behavior as expected of a phase transition. The use of a clean system with no cosolvents has allowed us to observe the retarding effects of phospholipid membranes. We study coaggregation between lipids and amyloid proteins in different stages from monomer to large fibrillar aggregates. For intermediate stages our emphasis is on the process rather than specific transient species along the pathway. The high reproducibility we have achieved allow us to study samples at well-defined stages along the pathway to represent a mixture of all transient species present at that tie point.

Non-covalent interactions in proteins

The protein folding-unfolding equilibrium is governed by a large number of non-covalent interactions under the constraints imposed by the covalent backbone. We have developed a method based on protein reconstitution from fragments that allows us to measure the relative contribution of different kinds of non-covalent interactions to protein assembly. Our results show clearly that interactions among hydrophobic side chains are by orders of magnitude more important than Coulombic interactions in protein folding and assembly, while repulsive electrostatic interactions play an important role in folding specificity by disfavoring unwanted conformations.

Stabilization of therapeutic proteins 

The therapeutic or technical value of a protein may increase if its stability towards denauration and degradation is enhanced. We have developed a general method for protein stabilization based on the thermodynamic coupling between protein folding and assembly from fragments. The method relies on fragment complementation and in vivo screening in a spit GFP system. A paper describing the method and demonstrating proof-of-principle was published in PNAS on Nov 1, 2010.

Protein folding through kinetic discrimination – MC simulations of amyloid formation

If protein folding occurred through random search through all possible conformation it would take longer than the life time of the universe – the Levinthal paradox. Using Monte Carlo simulations we have shown that protein folding can occur within very limited CPU time based on random search (association kinetics governed by closeness in space and equal for all kinds of contacts) if there is kinetic discrimination among formed contacts (slower average dissociation rate for native compared to non-native contacts). We are extending our algorithm towards simulations of amyloid formation from peptides, and investigate factors like sequence changes and the origin of sigmoidity in kinetic data.

Biological risks of nanoparticles

When nanoparticles enter a biological fluid (blood, lung fluid, etc.) their surface is rapidly covered by a corona of proteins. This corona defined the biological safety or risk of the nanoparticle, because it is the particle with its corona that the biological system responds to. We have shown that he corona around many nanoparticles is remarkably specific and contains a small number of proteins, and their relative surface concentration is very far from a random representation of their relative occurrence in the body fluid. Further, we study how the corona composition changes over time, or when the nanoparticle travles from on body compartment to another. We develop methodology to identify nanoparticle-associated proteins, and measure their interaction parameters. We study  nanoparticle-induced effects on protein aggregation and function. We connect our findings at the molecuar level to testable hypothesis on functoin sthat may be perturbed at physiological level. 


Undergraduate Courses2014:

Graduate Courses 2012-2013:

  • Surface plasmon resonance
  • Biophysical Chemistry of Proteins

Graduate Course 2009:

  • Optical spectroscopy for biomolecules

Academic Background

  • Professor of Molecular Protein Science (2009)
  • Professor of Physical Chemistry, Lund University (2004)
  • Associate professor of Physical Chemistry, Lund University (1999–2004)
  • Assistant professor of Physical Chemistry, Lund University (1993–1999)
  • Docent in Physical Chemistry, Lund University (1997)
  • PhD in Physical Chemistry, Lund University (1993)
  • MSc in Chemistry, Lund University and Stanford University (1985)


Activities for young adults with autism and mental retardation

Through a non-profit organization we organize housing and daily activities for young adults with autism and mental retardation. Our goal is a joyful and active existense where each individual is given a chance to develop according to his/her capacity with the assistance from a very stable group of personnel.


Children's book

Kjetil lär sig flyga. Kyrre Thalberg & Sara Snogerup Linse (2011)

Draksommar. Kyrre Thalberg & Sara Snogerup Linse (2012)

Kjetil och Jostein. Kyrre Thalberg & Sara Snogerup Linse (2013)

Prins Pralin åker Buss (2013)


Recent Scientific Publications (2007-2014)


1. Quantification of the Concentration of Aβ42 Propagons during the Lag Phase by an Amyloid Chain Reaction Assay. Arosio P, Cukalevski R, Frohm B, Knowles TP, Linse S. J Am Chem Soc. 2014:136:219-225. doi: 10.1021/ja408765u

2. Surface Effects on Aggregation Kinetics of Amyloidogenic Peptides. Vácha RLinse SLund M. J Am Chem Soc. 2014. doi: 10.1021/ja505502e

3. Solution conditions determine the relative importance of nucleation and growth processes in α-synuclein aggregation. Buell AK, Galvagnion C, Gaspar R, Sparr E, Vendruscolo M, Knowles TPJ, Linse S, Dobson CM. Proc Natl Acad Sci USA 2014:111:7671-7676. doi: 10.1073/pnas.1315346111

4. Differences in nucleation behavior underlie the contrasting aggregation kinetics of Aβ40 and Aβ42 peptides.  Meisl G, Yang X, Hellstrand E, Frohm B, Kirkegaard JB, Cohen SI, Dobson CM, Linse S, Knowles TP. Proc Natl Acad Sci USA 2014:111:9384-9389. doi: 10.1073/pnas.1401564111

5. Size-Dependent Effects of Nanoparticles on Enzymes in the Blood Coagulation Cascade. Sanfins E, Augustsson C, Dahlbäck B, Linse S, Cedervall T. Nano Lett. 2014. doi: 10.1021/nl501863u


6. Mathematical modeling of the protein corona: implications for nanoparticulate delivery systems.

Dell'Orco D, Lundqvist M, Linse S, Cedervall T. Nanomedicine (Lond). 2014:9:851-858. doi: 10.2217/nnm.14.39.

7. Charge dependent retardation of amyloid β aggregation by hydrophilic proteins.Assarsson A, Hellstrand E, Cabaleiro-Lago C, Linse SS. ACS Chem Neurosci. 2014:5:266-274. doi: 10.1021/cn400124r

8. Effects of Polyamino Acids and Polyelectrolytes on Amyloid β Fibril Formation. Assarsson A, Linse S, Cabaleiro-Lago C. Langmuir. 2014:30:8812-8818. doi: 10.1021/la501414j.


9. Aβ dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies. O'Malley TT, Oktaviani NA, Zhang D, Lomakin A, O'Nuallain B, Linse S, Benedek GB, Rowan MJ, Mulder FA, Walsh DM. Biochem J. 2014:461:413-426. doi: 10.1042/BJ20140219.


10. The chaperone domain BRICHOS prevents CNS toxicity of amyloid-β peptide in Drosophila melanogaster. Hermansson E, Schultz S, Crowther D, Linse S, Winblad B, Westermark G, Johansson J, Presto J. Dis Model Mech. 2014:7:659-665. doi: 10.1242/dmm.014787.



1. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Cohen SI, Linse S, Luheshi LM, Hellstrand E, White DA, Rajah L, Otzen DE, Vendruscolo M, Dobson CM, Knowles TP. Proc Natl Acad Sci U S A. 2013:110:9758-9763. doi:10.1073/pnas.1218402110

2. Membrane lipid co-aggregation with alpha-synuclein fibrils. Hellstrand E, Novacka A, Toppgaard D, Linse S, Sparr E. PLoS One 2013:8:e77235 (2013). doi: 10.1371/journal.pone.0077235

3. Adsorption of a-synuclein to supported bilayers: positioning and role of electrostatics. Hellstrand E, Grey M, Ainalem ML, Ankner J, Forsyth VT, Fragneto G, Haertlein M, Dauvergne MT, Nilsson H, Brundin P, Linse S, Nylander T, Sparr E. ACS Chem Neurosci. 2013:4:1339-1351.

4. Förster resonance energy transfer studies of calmodulin produced by native protein ligation reveal inter-domain electrostatic repulsion. Hellstrand E, Kukora S, Shuman CF, Steenbergen S, Thulin E, Kohli A, Krouse B, Linse S, Akerfeldt KS. FEBS J. 2013:280:2675-2687. doi: 10.1111/febs.12269. 


5. Calmodulin transduces calcium oscillations to differential target activation. Slavov N, Carey J, Linse S. ACS Chemical Neuroscience, 2013:4:601-12 DOI: 10.1021/cn300218d




6. Three-dimensional tracking of small aquatic organisms using fluorescent nanoparticles. Ekvall MT, Bianco G, Linse S, Linke H, Bäckman J, Hansson LA. PLoS One. 2013:8:e78498. doi: 10.1371/journal.pone.0078498

7. The BRICHOS Domain, Amyloid Fibril Formation, and Their Relationship. Knight SD, Presto J, Linse S, Johansson J. Biochemistry. 2013:52:7523-7531. doi: 10.1021/bi400908x

8. Calmodulin. O’Connell DJ. Bauer M, Marshall C, Ikura M, Linse S. In Encylopedia of Calcium Binding Proteins. Kretsinger, Ed. Springer. In press (2013)


9. Calbindin D28k. Åkerfeldt KS, Cedervall T, Bauer MC, Linse S. In Encylopedia of Calcium Binding Proteins. Kretsinger, Ed. Springer. In press (2013)




1. Food chain transport of nanoparticles affects behaviour and fat metabolism in top consumers. Cedervall T, Lard M, Hansson L-A, Linse S. PLoS One 7(2), e32254 (2012)

2. Calcium-dependent interaction of calmodulin with human 80S ribosomes and polyribosomes. Behnen P, David E, Delaney E, Frohm B, Bauer M, Cedervall T, O'Connell D, Akerfeldt KS, Linse S. Biochemistry 51:6718-6727 (2012)

 3. BRICHOS domains efficiently delay fibrillation of amyloid β-peptide. Wilander H, Presto J, Askarieh G, Biverstal H, Frohm B, Knight SD, Johansson J, Linse S. J. Biol. Chem. 287:31608-31617 (2012)

4. Role of Aromatic Side Chains in Amyloid β-Protein Aggregation. Cukalevski R, Boland B, Frohm B, Thulin E, Walsh D, Linse S. ACS Chem Neurosci. 3, 1008-1016 (2012)

 5. Polystyrene nanoparticles affecting blood coagulation. Oslakovic C, Cedervall T, Linse S, Dahlbäck B. Nanomedicine 8: 981-986 (2012)

 6. The effect of nanoparticles on Amyloid Aggregation Depends on the Protein Stability and Intrinsic Aggregation Rate. Cabaleiro-Lago C, Szczepankiewicz O, Linse S. Langmuir 28, 1852−1857 (2012)

 7. High affinity antibodies to Plasmodium Falciparum merozoite antigens are associated with protection from malaria. Reddy SB, Anders RF, Beeson JG, Färnert A, Kironde F, Berenzon SK, Wahlgren M, Linse S, Persson KEM, PLoS One 7:e32242.  (2012)

 8. Dynamics of conformational Ca(2+)-switches in signaling networks detected by a planar plasmonic device. Dell'Orco D, Sulmann S, Linse S, Koch KW. Anal Chem. 84:2982-2989 (2012)

 9. Delivery success rate of engineered nanoparticles in the presence of the protein corona: a systems-level screening. Dell'Orco D, Lundqvist M, Cedervall T, Linse S. Nanomedicine 8:1271-1281 (2012)

 10. Biocompatibility of Mannan Nanogel - Safe Interaction with Plasma Proteins. Ferreira SA, Oslakovic C, Cukalevski R, Frohm B, Dahlbäck B, Linse S, Gama FM, Cedervall T. BBA 1820:1043-51 (2012).

 11. Specific binding of a ß-cyclodextrin dimer to the amyloid ß peptide modulates the peptide aggregation process. Wahström A, Cukalevski R, Danielsson J, Jarvet J, Onagi H, Rebek J, Linse S, Gräslund A.  Biochemistry 51:4280-4289 (2012)



 1. Interactions in the native state of monellin, which play a protective role against aggregation. Szczepankiewicz O, Celia Cabaleiro-Lago C, Tartaglia GG, Vendruscolo M, Hunter T, Hunter GJ, Nilsson H, Thulin E, Linse S. Molecular Biosystems 7:521 – 532 (2011)

 2. Membrane interaction of α-synuclein in different aggregation states. Grey M, Linse S, Nilsson H, Brundin P, Sparr E. Journal of Parkinsons Disease 1:359-371 (2011)


3. Molecular Determinants of S100B Oligomer Formation  Thulin E, Kesvatera T, Linse S. PLOS ONE  6: e14768  (2011)

4. Monte Carlo simulations of protein amyloid formation reveal origin of sigmoidal aggregation kinetics. Linse B, Linse S. Molecular Biosystems 7:2296-2303 (2011)

5. Identification of a high-affinity network of secretagogin-binding proteins involved in vesicle secretion. Bauer MC. O’Connell D, Maj M, Wagner L, Cahill D, Linse S. Molecular Biosystems 7:2196-2204 (2011)

6. The structural role of N-linked glycans in human glypican-1. Svensson G, Hyrenius Wittsten A,  Linse S, Mani K. Biochemistry 50:9377-9387 (2011)

7. Structural changes in apolipoproteins bound to nanoparticles. Cukalevski R, Lundqvist M, Oslakovic C, Dahlbäck B, Linse S, Cedervall T. Langmuir 27:14360-14369 (2011)

8. Rapid and facile purification of apolipoprotein A-I from human plasma using thermoresponsive nanoparticles. Lundqvist M, Berggård T, Hellstrand E, Lynch I, Dawson KA, Linse S, Cedervall T. Journal of Biomaterials and Nanobiotechnology 2:258-266 (2011)

9. Probing calmodulin interactions using high-content protein arrays. O’Connell DJ, Bauer MC, Linse S, Cahill D. Methods Mol. Biol. 785:289-303 (2011)

10. Protein networks involved in vesicle fusion, transport and storage revealed by array-based proteomics. O’Connell DJ, Bauer MC, Linse S, Cahill D. Methods Mol. Biol. 781:47-58 (2011)



1. Aβ aggregation produces highly reproducible kinetic data and occurs by a two-phase process. Hellstrand E, Boland B, Walsh DM, Linse S. ACS Chem Neurosci. 1, 13-18 (2010) 

2. In vivo protein stabilization based on fragment complementation and a split GFP system Lindman S, Garcia-Hernandez A, Szczepankiewicz O, Frohm B, Linse S. Proc Natl Acad Sci U S A. 107, 19826-31 (2010) 

3. Retardation of Abeta fibril formation by phospholipid vesicles depends on membrane phase behavior. Hellstrand E, Sparr E, Linse S. Biophys J. 98:2206-2214 (2010)

4. Dual effect of amino modified polystyrene particles on A fibrillation. Cabaleiro-Lago C, Lynch I, Quinlan-Pluck F, Dawson K, Linse S. ACS Chem Neurosc, 1, 279-287 (2010)

5. pKa values for the unfolded state under native conditions explain the pH dependent stability of PGB1 Lindman S, Bauer MC, Lund M, Diehl C, Mulder FAA, Akke M, Linse S.. Biophys J, 99, 3365-73. (2010)

6. Integrated protein array screening and high throughput validation of 70 novel neural calmodulin binding proteins. O’Connell DJ, Bauer MC, O'Brien J, Johnson WM, Divizio CA, O'Kane SL, Berggård T, Merino A, Åkerfeldt KS, Linse S, Cahill DJ. Molecular and Cellular Proteomics, 9, 1118-1132 (2010)

        7. Calcium binding, structural stability and guanylate cyclase activation in GCAP1 variants associated with human cone dystrophy. Dell´Orco D, Behnen P, Linse S, Koch KW. Cell. Mol. Life. Sci. 67:973-984 (2010)

8. Modelling the time evolution of the nanoparticle-protein corona in a body fluid. Dell'Orco D, Lundqvist M, Oslakovic C, Cedervall T, Linse S. PLoS One. 5:e10949 (2010)

9. Inhibition of IAPP and IAPP(20-29) fibrillation by  polymeric nanoparticles. Cabaleiro-Lago C, Lynch I, Dawson KA, Linse S. Langmuir, 26:3453-3461 (2010)



1. A facile method for expression and purification of the Alzheimer disease-associated amyloid -peptide. Walsh DM, Thulin E, Minuogue A, Gustafsson T, Pang E, Teplow DB, Linse S. FEBS J. 276, 1266-1281 (2009)

2. Green fluorescence induced by EF-hand assembly in a split GFP system. Lindman S, Johansson I, Thulin E, Linse S. Protein Sci. 18:1221-1229 (2009)


3. Complete High Density Lipoproteins in Nanoparticle Corona. Hellstrand E, Lynch I, Andersson A, Drakenberg T, Dahlbäck B, Dawson KA, Linse S, Cedervall T. FEBS J. 276:3372-3381 (2009)


4. Protein GB1 Folding and Assembly from Structural Elements. Bauer MC, Xue WF, Linse S. Int. J. Mol. Sci. 10, 1552-1566 (2009)


5. Role of protein surface charges in monellin sweetness. Xue WF, Szczepankiewicz O, Thulin E, Linse S, Carey J. Biochim Biophys Acta. 1794, 410-20 (2009)


6. Chemical and Thermal Unfolding of Glypican-1: Protective Effect of Heparan Sulfate Against Heat-Induced Irreversible Aggregation. Svensson G, Linse S,Mani K. Biochemistry 48:9994-10004 (2009)




1. Inhibition of amyloid beta protein fibrillation by polymeric nanoparticles. Cabaleiro-Lago C, Quinlan-Pluck F, Minogue A, Lynch I, Dawson KA, Walsh DM, Linse S.  J Am Chem Soc, 130, 15437-15443 (2008)


2. Structure and functional properties of the Bacillus subtilis transcriptional repressor Rex. Wang E, Bauer MC, Rogstam A, Linse S, Logan DT, von Wachenfeldt C. Molecular Microbiology 69, 466-478 (2008)


3. Calmodulin binding to the polybasic C-termini of STIM proteins involved in store operated

calcium entry. Bauer MC, O’Connell D, Cahill DJ, Linse S. Biochemstry (Rapid Report) 47, 6089-6091 (2008)


4. Effects of metal binding loop mutations on calcium binding to integrin-binding protein. 1. Evolution of the EF-hand. Yamniuk A, Gifford J, Linse S, Vogel H. Biochemistry, 47, 1696-1707 (2008)


5. Zn2+ binding to human calbindin D28k. Bauer MC, Frohm B, Malm J, Groves P, Linse S. Protein Science 17:760-767 (2008)


6. Molecular Design of Specific Metal-Binding Peptide Sequences from Protein Fragments: Theory and Experiment. Kožíšek M, Svatoš A, Buděšínský M, Muck A, Bauer MC, Kotrba P, Ruml T, Havlas Z, Linse S, Rulíšek L. Chemistry, 14, 7836-7846 (2008)


7. Protein interaction, association and fibrillation. Linse S. in Systems Chemistry. Proceedings of the International Beilstein symposium. Hicks and Kettenr, Eds. 183-194 (2008)


8. Biologiska risker med nanopartilkar. Cedervall T, Lindman S, Thulin E, Berggård T, Linse S. Kemivärlden Bioctech.  (2008)




1. Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Cedervall, T, Lynch I, Lindman S, Berggård T, Thulin E, Nilsson H, Dawson KA, Linse S. Proc Natl Acad Sci U S A. 104, 2050-2055 (2007)  Cozzarelli Prize by PNAS for outstanding scientific achievement during 2007.


2. Nucleation of protein fibrillation by nanoparticles. Linse S, Cabaliero-Lago C, Xue W-F, Lynch I, Lindman S, Thulin E, Radford SR, Dawson KA. Proc Natl Acad Sci U S A. 104, 8691-8696 (2007)


3. Detailed Identification of Plasma Proteins Absorbed to Copolymer Nanoparticles. Cedervall T, Lynch I, Foy M, Berggård T, James P, Donnelly SC, Cagney G, Linse S, Dawson KA. Angewandte Chemie Int. Ed. 46, 5754-5756 (2007)

4. Protein folding through kinetic discrimination. Linse S, Linse B. J Am Chem Soc 129, 8481-8486 (2007)


5. Residue-specific pKa determination of lysine and arginine side chains by indirect 15N and 13C NMR: Application to apo calmodulin. André I, Linse S, Mulder FAA. J Am Chem Soc, 129: 15805-15813 (2007)


6. Systematic invesitigation of the thermodynamics of HSA adsorption to N-iso-propylacrylamide N-tert-butylacrylamide copolymer nanoparticles. Effects of particle size and hydrophobicity. Lindman S, Lynch I, Thulin E, Nilsson H, Dawson KA, Linse S. Nanoletters 7, 914-20 (2007)


7. Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin. Rogstam A, Linse S, Lindqvist A, James P, Wagner L, Berggård T. Biochem J. 401, 353-363 (2007)


8. pK (a) values for side-chain carboxyl groups of a PGB1 variant explain salt and pH-dependent stability. Lindman S, Linse S, Mulder FA, Andre I. Biophys J. 92, 257-66 (2007)


9. Structural properties of semenogelin I. Malm J, Jonsson M, Frohm B, Linse S. FEBS J. 274, 4503-4510 (2007)


10. Production and physicochemical characterization of acidocin D20079, a bacteriocin produced by Lactobacillus acidophilus DSM 20079. Deraz S, Hedström M, Karlsson EN, Linse S, Khalil AA, Mathiasson B. World Jornal of Microbiology & Bioctechnology 23, 911-921 (2007)


11. Methods for detection and analysis of protein-protein interactions. T Berggård, P James, S Linse. Proteomics 7: 2833-2842 (2007)


12. Protein reconstitution and three-dimensional domain swapping. Limits and benefits of covalency. Carey J, Lindman S, Bauer M, Linse S. Protein Science 16: 2317-2333 (2007)


13.  The nanoparticles-protein complex as a biological entity; a complex fluids and surface science challenge for the 21st century. Lynch I, Cedervall T, Lundqvist M, Cabaleiro-Lago C, Linse S, Dawson K. Adv. Colloid. Interface. Sci. 134-35: 167-174 (2007)


Former Ph D students

Jonas Fast, thesis 2004

Ingemar André, thesis 2005

Wei-Feng Xue, thesis  2005

Stina Lindman, thesis 2010 

Mikael Bauer, thesis 2010

Olga Szczepankievicz, thesis 2011

Erik Hellstrand, thesis 2012


Former post docs

Tord Berggård

Christophe Vanbelle

Tommy Cedervall

Charlotte Helgstrand

Cynthia Shuman

Daniele Dell'Orco

Petra Behnen

Jonas Persson

Marie Grey