Research Interests

DNA carries all the information needed for survival and reproduction of a cell. This information is physically encoded by forming chains of nucleotides (A,C,G,T) in a specific order, thus obtaining a four-letters encoding string. The well-known double helix in which these chains are geometrically organized is far from being homogeneous. Experimental evidence shows indeed that the actual geometry locally deviates from an ideal double-helix, according to the sequence of the fragment under inspection. Thus, the composition of the DNA molecule is also reflected into its specific conformational features, which in turn evidence the presence of sequence- dependent elastic properties. These features play a key role in promoting or inhibiting the interaction with the protein machinery of the cell, thus ultimately affecting the epigenetic regulation of DNA and the emergence of diseases should such regulation fail.
More recently, the role of RNA has also been shown to be more widespread than envisaged previously. For instance, it has been demonstrated that long non-coding RNAs have key regulatory effects in the cell, yet their molecular description is far from being clear. This is due to the single-stranded nature of the RNA typically found in the cell and to the presence of many weak interactions, which confer to this molecule a rich conformational heterogeneity.
Our current research line is focused on investigating the sequence-dependent molecular properties of DNA and RNA, and their role in biocellular processes. For instance, via atomistic simulations we have uncovered the change in the elasticity response of double-stranded nucleic acids, finding that dsDNA becomes stiffer while dsRNA becomes softer upon pulling. We have also shown that the stretching elasticity of dsDNA is a universal function of its local minimum-energy conformation.
We also look at larger molecules via coarse-grained approaches. For instance, we have developed the coarse-grained model MADna, which provides an accurate sequence-dependent description of the elasticity and conformation of double-stranded DNA based on an extensive dataset of all-atom simulations. At even larger scales, we have employed coars(er)-grained descriptions of topologically-bound membranes, inspired by the kinetoplasts observed in certain parasytes, and observed the emergence of spontaneous Gaussian curvature induced by the linking chirality.

Lipidic mesophases are interesting objects obtained by mixing water and lipids in suitable proportions. Depending on the specific details of the lipids employed as well as on lipid concentration and temperature, mesophases with different microscopic structures are obtained, including arrangements as hexagonal, lamellar and cubic phases. Lipidic mesophases are at the center of intense research due to many different applications, most of which are based on the molecular transport within these systems (see our review for more info). Our research on the topic is focused on understanding the interplay between structure and transport, with the goal of providing a reliable theoretical framework for devising related applications with tailored properties.
For example, in a paper we have provided the necessary theoretical framework to analyze the results of the so-called diffusion setup. Comparison of the theoretical predictions against experimental data from systems with known features shows an excellent quantitative agreement without any adjustable parameter, thus appointing our theory as a reliable tool for data analysis. We employed a similar approach to assess the effect of digestion of lipid heads by bacterial enzymes, which allowed a quantitative description of the slowing down of drug delivery from mesosomes observed along digestion by bacteria found in the human microbiome.
The nanoconfining environment provided by lipid mesophases also affects the properties of water, which shows a highly exotic behavior. For instance, disordered lipid phases can prevent water crystallization down to very low temperature, thus suggesting a possible mechanism of life survival at subzero temperatures. Also the hydrogen-bond structure and the diffusion of water are strongly affected by nanoconfinement, yet their behavior follows general rules dictated by the geometry of the nanochannels.
The local geometry affects also the large-scale diffusion, as shown by our Brownian Dynamics simulations . We showed that the effective diffusion coefficient is regulated by a subtle interplay between curvature and bottlenecks of the network of water channels. The results from this study can be used by experimental researchers to estimate the diffusion coefficient of a molecule diffusing within a cubic phase of interest. To ease such application, you can find here a tool that computes the effective diffusion coefficient starting from the structural parameters of the cubic phase. Yet, the shape of the nanochannels is only part of the story, since molecular transport is also highly dependent on the exotic properties of nanoconfined water. At the moment, this effect has been implemented in the tool by introducing an estimation of the thickness ot the layer of almost-immobilized water.
Lipidic Cubic Phases also provide good environments for enzymatic reactions. For example, we have studied how the activity of the enzyme aldolase is enhanced when within a cubic phase and, based on the known structure of the enzyme and of mesophases, we suggested a microscopic picture of how such an enhancement can be achieved. The level of confinement as well as the nontrivial mobility features of water in nanochannels qualitatively and quantitatively affect the features of the enzymatic products (have a look at this article), providing useful tools for related applications, e.g. as biomarkers.

Molecular chaperones are proteins whose role in the cell is, loosely speaking, to help out other proteins. Among them, the heat-shock protein Hsp70 is a versatile tool, as it has been shown to be involved in many cellular processes such as protein import into organelles, aid in folding out of ribosomes, prevention of misfolding or help in dissociating protein complexes. We are interested in giving a microscopic explanation and quantification to these tasks, based on coarse-grained molecular dynamics simulations. For example, we have determined the effective thermodynamic force exerted by Hsp70 in protein import and outlined its essential role to achieve complete translocation in time windows compatible with the cell cycle. Combininig our coarse-grained simulations with a biochemical network model, we have also addressed the molecular details of the action of Hsp70 as unfoldase, a key role aimed at preventing protein misfolding and aggregation, and quantified the effective efficiency of Hsp70 in transducting chemical energy into mechanical work. The coarse-grained simulations have also elucidated the mechanism behind the limited aggregation observed for a novel essay introduced to inspect the action of Hsp70.

Amyloid fibrils are proteinaceous aggregates first identified in neurodegenerative diseases such as Alzheimer's or Parkinson's, although they are now being investigated for many biotechnological applications. In a work, we unveiled the existence of universal laws characterizing the periodic properties of various fibril families at length scales of tens to hundreds of nanometers. More recently, we have also reported the rich polymorphism of insulin-based fibrils, providing a classification based on their mesoscale structure and "selection rules" for the hierarchical formation of fibrils based on geometrical arguments.
Further studies have focused on cholesteric liquid droplets formed by amyloid fibrils, for which we provided a theoretical construction recapitulating the distinct families observed in experiments according to the volume of the droplet, or on the effect of simultaneous application of a pulling force and nanoconfinement on amyloid fibrils.

Publications List

1. Lipidic drug delivery systems are responsive to the human microbiome
   J. Caukwell, S. Assenza, K. A. Hassan, B. A. Neilan, A. J. Clulow, L. Salvati Manni and W.-K. Fong
   J. Coll. Interf. Sci. 677, 293 (2025)
   


2. Shape and size tunability of sheets of interlocked ring copolymers
   J. Luengo-Márquez*, S. Assenza and C. Micheletti
   Soft Matter 20, 6595 (2024) ( *Co-corresponding Author )
   


3. Universality in the Structure and Dynamics of Water under Lipidic Mesophase Soft Nanoconfinement
   E. Zunzunegui-Bru, S. R. Alfarano, P. Zueblin, H. Vondracek, F. Piccirilli, L. Vaccari, S. Assenza* and R. Mezzenga
   ACS Nano 18, 21376 (2024) ( *Co-corresponding Author )
   


4. Hierarchical Protofilament Intertwining Rules the Formation of Mixed-Curvature Amyloid Polymorphs
   J. Zhou, S. Assenza* , M. Tatli, J. Tian, I. M. Ilie, E. L. Starostin, A. Caflisch, T. P. J. Knowles, G. Dietler, F. S. Ruggeri, H. Stahlberg, S. K. Sekatskii and R. Mezzenga
   Adv. Sci. 11, 2402740 (2024) ( *Co-first Author )
   


5. Systematic comparison of atomistic force fields for the mechanical properties of double-stranded DNA
   C. Roldán-Piñero, J. Luengo-Márquez , S. Assenza* and R. Pérez
   J. Chem. Theory Comput. 20, 2261 (2024) ( *Co-corresponding Author )
   


6. RNA multiscale simulations as an interplay of electrostatic, mechanical properties, and structures inside viruses
   S. Cruz-León, S. Assenza, S. Poblete and H. V. Guzman
   Book chapter in Physical Virology. Springer Series in Biophysics, vol 24 - Editors M. Comas-García and S. Rosales-Mendoza (2023)
   


7. Unusual phosphatidylcholine lipid phase behavior in the ionic liquid ethylammonium nitrate
   L. Salvati Manni, C. Davies, K. Wood, S. Assenza, R. Atkin and G. G. Warr
   J. Coll. Interf. Sci. 643, 276 (2023)
   


8. Force-dependent elasticity of nucleic acids
   J. Luengo-Márquez, J. Zalvide-Pombo, R. Pérez and S. Assenza
   Nanoscale 15, 6738 (2023)
   


9. Interplay of Hydropathy and Heterogeneous Diffusion in the Molecular Transport Within Lamellar Lipid Mesophases
   A. M. Bosch and S. Assenza
   Pharmaceutics 15, 573 (2023)
   


10. A fluorescent multi-domain protein construct reveals the individual steps of the unfoldase action of Hsp70
    S. Tiwari, B. Fauvet, S. Assenza, P. De Los Rios and P. Goloubinoff
    Nature Chem. Biol. 19, 198 (2023)
    


11. Intermolecular forces at ice and water interfaces: Premelting, surface freezing, and regelation
    J. Luengo-Márquez, F. Izquierdo-Ruiz and L. G. MacDowell
    J. Chem. Phys. 157, 044704 (2022)
    


12. Accurate sequence-dependent coarse-grained model for conformational and elastic properties of double-stranded DNA
    S. Assenza and R. Pérez
    J. Chem. Theory Comput. 18, 3239 (2022)
    


13. Analytical theory for the crossover from retarded to non-retarded interactions between metal plates
    J. Luengo-Márquez* and L. G. MacDowell
    J. Phys.: Condens. Matter. 34, 275701 (2022) ( *Co-corresponding Author )
    


14. Enzymatic hydrolysis of monoacylglycerols and their cyclopropanated derivatives: Molecular structure and nanostructure determine the rate of digestion
    L. Salvati Manni, M. Duss, S. Assenza, B. J. Boyd, E. M. Landau and W.-K. Fong
    J. Coll. Interf. Sci. 588, 767 (2021)
    


15. Interplay between confinement and drag forces determine the fate of amyloid fibrils
    K. B. Smith, M. Wehrli, A. Japaridze, S. Assenza, C. Dekker and R. Mezzenga
    Phys. Rev. Lett. 124, 118102 (2020)
    


16. Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
    S. Assenza, A. S. Sassi, R. Kellner, B. Schuler, P. De Los Rios and A. Barducci
    eLife 8, e48491 (2019)
    


17. Six-fold director field configuration in amyloid nematic and cholesteric phases
    M. Bagnani, P. Azzari, S. Assenza and R. Mezzenga
    Sci. Rep. 9, 12654 (2019)
    


18. Soft condensed matter physics of foods and macronutrients
    S. Assenza and R. Mezzenga
    Nature Reviews Physics 1, 551 (2019)
    (Click here to access it for free)
    


19. Spatiotemporal Control of Enzyme‐Induced Crystallization Under Lyotropic Liquid Crystal Nanoconfinement
    J. J. Vallooran, S. Assenza and R. Mezzenga
    Angew. Chem. Int. Ed. 58, 7289 (2019)
    


20. Impact of Molecular Partitioning and Partial Equilibration on the Estimation of Diffusion Coefficients from Release Experiments
    R. Ghanbari, S. Assenza*, P. Zueblin and R. Mezzenga
    Langmuir 35, 5663 (2019) ( *Co-first author )
    


21. Soft biomimetic nanoconfinement promotes amorphous water over ice
    L. Salvati Manni, S. Assenza*, M. Duss, J. J. Vallooran, F. Juranyi, S. Jurt, O. Zerbe, E. M. Landau and R. Mezzenga
    Nature Nanotechnology 14, 609 (2019) ( *Co-first author )
    


22. The interplay of channel geometry and molecular features determines diffusion in lipidic cubic phases
    R. Ghanbari, S. Assenza and R. Mezzenga
    J. Chem. Phys. 150, 094901 (2019)
    


23. Confinement‐Induced Ordering and Self‐Folding of Cellulose Nanofibrils
    K. B. Smith, J.‐N. Tisserant, S. Assenza, M. Arcari, G. Nyström and R. Mezzenga
    Adv. Sci. 6, 1801540 (2019)
    


24. Efficient Asymmetric Synthesis of Carbohydrates by Aldolase Nano-Confined in Lipidic Cubic Mesophases
    T. Zhou, J. J. Vallooran, S. Assenza, A. Szekrenyi, P. Clapés and R. Mezzenga
    ACS Catal. 8, 5810 (2018)
    


25. Curvature and bottlenecks control molecular transport in inverse bicontinuous cubic phases
    S. Assenza and R. Mezzenga
    J. Chem. Phys. 148,054902 (2018)
    
26. Shape of a Stretched Polymer
    A. S. Sassi, S. Assenza* and P. De Los Rios
    Phys. Rev. Lett. 119, 037801 (2017) ( *Corresponding Author )
    
27. Diffusion of Polymers through Periodic Networks of Lipid-Based Nanochannels
    R. Ghanbari, S. Assenza*, A. Saha and R. Mezzenga
    Langmuir 33,3491 (2017) ( *Co-first author )
    
28. Quantifying the transport properties of lipid mesophases by theoretical modelling of diffusion experiments
    L. M. Antognini, S. Assenza, C. Speziale and R. Mezzenga
    J. Chem. Phys. 145,084903 (2016)
    
29. Quantifying the role of chaperones in protein translocation by computational modeling
    S. Assenza*, P. De Los Rios and A. Barducci
    Front. Mol. Biosci. 2,8 (2015) ( *Co-corresponding Author )
    
30. Universal Behavior in the Mesoscale Properties of Amyloid Fibrils
    S. Assenza, J. Adamcik, R. Mezzenga and P. De Los Rios
    Phys. Rev. Lett. 113, 268103 (2014)
    
31. Emerging Meso- and Macroscales from Synchronization of Adaptive Networks
    R. Gutiérrez, A. Amann, S. Assenza, J. Gómez-Gardeñes, V. Latora, and S. Boccaletti
    Phys. Rev. Lett. 107, 234103 (2011)
    
32. Emergence of structural patterns out of synchronization in networks with competitive interactions
    S. Assenza, R. Gutiérrez, J. Gómez-Gardeñes, V. Latora, and S. Boccaletti
    Sci. Rep. 1,99 (2011)
    
33. Enhancement of cooperation in highly clustered scale-free networks
    S. Assenza, J. Gómez-Gardeñes and V. Latora
    Phys. Rev. E 78,017101 (2008)
    

Software Tools

Structural info of mesophases

Diffusion Coefficient in Water Channels

Here you can find some tools that we developed. Click on the image of the tool to use it (in some cases, you will be redirected to a GitHub page). The tools can be freely used, and relevant references are listed for each of them. Please cite the appropriate articles if you use the tools in your research!

Structural info of mesophases

Diffusion Coefficient in Water Channels

Mechanically-accurate DNA (MADna)

Open Positions

We always welcome inquiries from prospective PhD students or postdocs interested in joining us to pursue nice research projects. Get in touch to discuss possible funding opportunities offered by national and international programs.

Current Members

Salvatore Assenza

Principal Investigator

Módulo 5 (Office 501), Facultad de Ciencias, C/ Francisco Tomás y Valiente 7, 28049 Madrid (Spain)

I grew up in the cozy city of Modica, part of a UNESCO Heritage Site in the southmost part of Sicily (you may want to check it out for your next vacation, it will be a wonderful experience for both your eyes and your tummy!)

I carried out my undergraduate studies in Physics at the University of Catania, where I obtained my BSc (2008) and MSc Degrees (2010). In parallel, I attended Scuola Superiore di Catania, an excellence center within University of Catania where, after a competitive selection based on written and oral exams, 20 students selected within the whole University (independently of the discipline) receive a scholarship for the whole duration of their studies and attend additional courses aimed at boosting an early start of their research activity. This was the spark for my interest in a career as a researcher, as I had the possibility to interact with Prof. Latora and Prof. Gómez, with whom I pursued a prolific investigation vein on evolutionary dynamics and synchronization in Complex Networks.

This interest in complexity brought me to start a PhD in Physics (2011-2015) at EPF Lausanne supervised by Prof. De Los Rios and Dr. Barducci. There, I studied biomolecular systems under the lens provided by polymer physics, with focus on amyloid fibrils and molecular chaperones, and learned the foundations of soft matter and molecular simulations.

This background was extremely useful for my subsequent Postdoctoral experience (2015-2018) as a theorist in the group of experimentalists led by Prof. Mezzenga at ETH Zürich. There, I have reinforced my view that theory and experiment have a lot to earn, and learn, from a continuous interchange of views, as can be seen from my scientific production in this period. At ETH, I focused mainly on lipid-based mesophases, a class of materials apt for drug-delivery purposes. Such applications need a thorough understanding of the molecular diffusion within mesophases, which I have put on solid theoretical bases by providing both a theoretical framework to analyze experiments and simulation-based predictions in agreement with experiments, which enabled developing a tool to estimate the diffusion coefficient of a molecule within cubic phases from the knowledge of their structure. Apart from this main investigation line, I also worked actively in other soft-matter systems, such as amyloid-based cholesteric liquid crystals and cellulose nanofibrils.

Later, I was a Postdoc (2019-2020) in the group led by Prof. Pérez at Universidad Autónoma de Madrid and IFIMAC, where I worked on the microscopical origin of the mechanical properties of DNA, with focus on their sequence dependence.

Starting from the end of 2020, I am pursuing my own research line at IFIMAC focused on the theoretical study of several biophysical and biocellular phenomena. I have been first supported by a Junior Leader Fellowship from la Caixa Foundation jointly with the Marie Skłodowoska-Curie program (2020-2023). Since January 2024, I am counting on the support of the Spanish Agency for Research as a Ramón y Cajal Fellow.

Juan Luengo Márquez

PhD Student

Módulo 8 (Office 401-3), Facultad de Ciencias, C/ Francisco Tomás y Valiente 7, 28049 Madrid (Spain)

I studied a Bachelor's degree in Chemistry at the Complutense University of Madrid, where I specialized in Physical Chemistry. Afterwards, I studied the Master's degree in Condensed Matter Physics and Biological Systems at the Autónoma University of Madrid. During this period, my research interests channeled towards Statistical Physics, Thermodynamics, Computer Simulations, and Soft Matter Physics in general.

From 2018 to 2021, starting with my Bachelor's thesis, I carried out my research under the supervision of Prof. Luis G. MacDowell (Complutense U.), within the framework of the theoretical exploitation of the Lifshitz theory of the van der Waals forces.

From the beginning of 2021, I joined Dr. Salvatore Assenza's group, under whose supervision I develop my PhD thesis on the investigation of the mechanical properties of nucleic acids through Molecular Dynamics simulations and theoretical methods.

Currently, I am a member of the Instituto Nicolás Cabrera, and since early 2022, I earned a position as non-doctor assistant professor at the Department of Theoretical Condensed Matter Physics of the Autónoma University of Madrid.

Finally, my broadly neglected hobbies include classical literature, playing basketball, and blundering at chess.

Eva Zunzunegui Bru

PhD Student

LFO E25, IFNH, Schmelzbergstrasse 9, 8092 Zürich (Switzerland)

I come from Madrid, where I pursued my bachelor studies in Physics in Universidad Autónoma. In my third year of bachelor I participated in the Erasmus programme in Universität Wien. That summer I had my first experience with computational research of microscopic systems together with Prof. Christos Likos in Vienna. Later on I completed my Masters in condensed matter physics in Universidad Autónoma de Madrid in june 2019. From November 2019 to June 2020 under the supervision of Dr. Tomás González Lezana I obtained a research position in CSIC to study helium nanodroplets under simulation with path integral monte carlo. This experience reinforced my computational skills and my enthusiasm to learn more about computer simulations. Currently I am doing my phd in ETH Zürich under the supervision of Prof. Raffale Mezzenga and Dr. Salvatore Assenza on the study of the properties of water under nanoconfinement in lipid-based mesophases by means of atomistic molecular dynamics simulations. In ETH I share my ideas with my experimentalist collegues, this is a great opportunity to expand my knowledge about the system, I am always ready to learn new things about the fascinating world of biomolecular systems!

Teaching Notes

These notes are licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License

Present and Past Collaborators

Fernando Moreno Herrero
Centro Nacional de Biotecnología - CSIC (Spain)

Laura R. Arriaga
IFIMAC & Universidad Autónoma de Madrid (Spain)

Juan Aragonés
IFIMAC & Universidad Autónoma de Madrid (Spain)