Amyloid-â peptide (Aâ) isoforms of different lengths and aggregation propensities coexist in vivo. These different isoforms are able to nucleate or frustrate the assembly of each other. Nterminal truncated Aâ(11-40) and Aâ(11-42) make up one fifth of plaque load yet nothing is known about their interaction with full-length Aâ(1-40/42). Here we show that in contrast to C-terminal truncated isoforms which do not co-fibrillise, deletions of ten residues from the N-terminus of Aâ have little impact on its ability to co-fibrillise with the full-length counterpart. As a consequence N-terminal truncated Aâ will accelerate fibre formation and co-assemble into short rod-shaped fibres with its full-length Aâ counterpart. Furthermore we show Cu2+ forms a very tight tetragonal complex with truncated Aâ(11-40) with a femtomolar affinity. These observations have implications for the assembly kinetics, morphology and toxicity of all Aâ isoforms. The process by which amyloid-â (Aâ) disrupts synaptic activity, and causes neuronal cell death in Alzheimer’s disease remains poorly understood. A potential mechanism of toxicity is in the ability of Aâ to form, membrane-spanning ion channels. However, there has been a mismatch between the channel forming properties of Aâ isoforms, 40 and 42 amino acids long, and their known relative pathogenicity. We observe ion channel formation by oligomeric Aâ42, but also show Aâ40 does not form ion channels in cellular membranes. This makes a strong link between ion channel formation and the pathology of Aâ isoforms. Molecules that block these ion channels may represent therapeutic targets. [1] Ion Channel Formation by Amyloid-â42 Oligomers but not Amyloid-â40 in Cellular Membranes DC Bode, MD Baker, JH Viles* (2017) J of Biol Chem 292, 1404-1413 [2] Truncated Amyloid-â (11-40/42) from Alzheimer's Disease Binds Copper2+ with a Femtomolar Affinity and Influences Fibre Assembly J D Barritt, J H. Viles* (2015) J of Biol Chem, 290, 27791-27802 [3] The Rapid Exchange of Zinc2+ Enables Trace Levels to Profoundly Influence Amyloid-â Misfolding and Dominates Assembly Outcomes in Cu2+/Zn2+ Mixtures C J Matheou, N D Younan, J H Viles* (2016) J Mol Biol 428, 2832-2846

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

The protein Lgl (Lethal giant larvae) is part of a conserved protein complex, which is responsible for the asymmetric localisation of cell-fate determinants, for instance, in Drosophila SOP precursor cells. We formulate continuum models, which consider the phosphorylated and the unphosphorylated conformations of Lgl within the cell cytoplasm and on the cell cortex. After presenting illustrative numerical simulations, we prove first the equilibration of the underlying complex-balance volumesurface reaction-diffusion system and perform further a rigorous quasi-steady-state-approximation in a fast-reaction limit.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Angélique Igel-Egalon1¶, Mohammed Moudjou1¶, Florent Laferrière1¶, Tina Knäpple1, Laetitia Herzog1, Fabienne Reine1, Hubert Laude1, Human Rezaei1*, Vincent Béringue1* 1VIM, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France ¶Equal contributors, *Senior authorship Mammalian prions are proteinaceous pathogens responsible for fatal, neurodegenerative disorders in human and animals. They are formed of misfolded assemblies (PrPSc) of the host-encoded cellular prion protein (PrPC). In the infected species, prions replicate by seeding the conversion and polymerization of host PrPC. Distinct prion strains are recognized within the same host-species, exhibiting defined PrPSc biochemical properties and stereotyped biological traits. While strain information is encoded within the conformation of PrPSc assemblies, the storage of the structural information and the molecular requirements for self-perpetuation remain uncertain. In particular, the polymerization steps and its dynamic nature remains mostly hypothetical. It is widely believed that monomeric PrPC is constantly recruited within the forming aggregates allowing PrPSc fibril growth. Fibril fragmentation is supposed to provide further converting seeds, favouring prion exponential replication. Whether this proposed mechanism is versatile or strain-dependent remains to be determined, as is the real contribution of fragmentation. We have investigated this issue by analysing the dynamic of PrPSc assembling during cell-free prion amplification by protein misfolding cyclic amplification (PMCA). We show that: i) prion amplification occurs through preferential amplification of small oligomeric forms of PrPSc that can further assemble into larger aggregates; ii) disassembling rather than fragmentation sustains the self-perpetuation of the process, iii) different prion strains exhibit similar amplification dynamic. Thus, prion replication may proceed through an assembly/disassembly process.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

This work is motivated by protein aggregation phenomena in neurodegenerative diseases. A key observation of in-vitro spontaneous polymerization experiments of prion protein is the large variability of the so-called 'nucleation time', which is experimentally defined as the lag time before the polymerization of proteins truly starts (typically several hours in a 10-20 hours experiment). In this context, we study a stochastic version of a well-known nucleation model in physics, namely the Becker-Döring model [1]. In this model, aggregates may increase or decrease their size one-by-one, by capturing or shedding a single monomer particle. We will present numerical and analytical investigation of the nucleation time defined as a first passage time problem [2, 3]. Finally, we will present limit theorem techniques to study the link from the discrete size Becker-Döring model to a continuous size version (the Lifshitz-Slyozov model), which may be of importance to study large size aggregates formation. For general coefficients and initial data, we introduce a scaling parameter and show that the empirical measure associated to the Becker-Döring system converges in some sense to the Lifshitz-Slyozov equation when the scaling parameter goes to 0. When the aggregation is favorable, we derive a mean-field transport PDE limit together with an entrant boundary condition, leading to an effective reduced dynamical model [4]. When the aggregation is initially unfavorable, we shed light on metastable behavior and phase transition phenomena. [1] E. Hingant, R. Y., arXiv:1609.00697 (2016). [2] R. Y., M. R. D'Orsogna, and T. Chou. J. Chem. Phys., 137:244107, (2012). [3] R. Y., S. Bernard, E. Hingant, L. Pujo-Menjouet, J. Chem. Phys., 144(3):034106, (2016). [4] Julien Deschamps, Erwan Hingant, R.Y., arXiv:1605.08984 (2016).

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Cassandra Terrya Adam Wenborna Nathalie Grosa Jessica Sellsa Susan Joinera Laszlo L.P. Hosszua M. Howard Tattuma Silvia Panicob Daniel K. Clareb, John Collingea, Helen R. Saibilb and Jonathan D.F. Wadswortha* a, MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK b, Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK Prions cause lethal neurodegenerative diseases in mammals, including scrapie in sheep and goats, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt–Jakob disease (CJD) in humans. Mammalian prions are hypothesised to be fibrillar or amyloid forms of prion protein (PrP) which self-propagate by means of seeded protein polymerisation but structures observed had not been definitively correlated with infectivity and the three-dimensional structure of prions remained unknown. We developed new methods to obtain pure preparations of intact prions from mouse brain1 and showed that pathogenic PrP is assembled into rod-like assemblies (PrP rods) that faithfully transmit prion strain-specific phenotypes when inoculated into mice. We have utilised the precision of cell culture prion infectivity assays to define the physical relationship between PrP rods and prion infectivity and used electron tomography to define their architecture. Our 3D analysis2 demonstrates that ex vivo infectious PrP rods from different strains observed have a common hierarchical assembly comprising twisted pairs of short fibres with repeating substructure which are markedly different to non-infectious PrP fibrils generated in vitro. References 1. A. Wenborn, C. Terry, N. Gros, S. Joiner, L. D’Castro, S. Panico, J. Sells, S. Cronier, J. Linehan, S. Brandner, H.R. Saibil, J. Collinge, J.D.F Wadsworth, Sci. Rep. A novel and rapid method for obtaining high titre intact prion strains from mammalian brain, 2015, 5, 10062. C. Terry, A. Wenborn, N. Gros, J. Sells, S. Joiner, L.L.P Hosszu, M.H. Tattum, S. Panico, D.K. Clare, J. Collinge, H.R. Saibil, J.D.F Wadsworth. Open Biology. Ex vivo mammalian prions are formed of paired double helical prion protein fibrils, 2016, 6, 160035.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

In a previous work by Alvarez-Martinez et al. (2011), the authors pointed out some fallacies in the mainstream interpretation of the prion amyloid formation. It appeared necessary then to propose an original hypothesis able to reconcile the in vitro data with the predictions of a mathematical model describing the problem. The model presented here, has been developed accordingly with the hypothesis that an intermediate on-pathway leads to the conformation of the prion protein into an amyloid competent isoform thanks to a structure, called micelles, formed from hydrodynamic interaction. Experimental data have been compared to the prediction of our model leading to a new hypothesis for the formation of infectious prion amyloids. In the last part, we will introduce a new model describing another dangerous liaison: the interaction between prion proteins and Abeta peptides that may lead to Alzheimer’s disease.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Autophagosomes are double membrane-bound organelles that are formed de novo during a process called autophagy. Autophagosomes mediate the bulk degradation of cytoplasmic material such as aggregated proteins, dysfunctional or surplus mitochondria and intracellular pathogens. Autophagy is conserved from yeast to human and has been shown to protect the organism from conditions such as starvation, neurodegeneration and infectious diseases. During autophagosome formation initially small membrane structures termed isolation membranes are formed. These isolation membranes expand and thereby gradually enclose cytoplasmic cargo. Finally, isolation membranes close to give rise to mature autophagosomes. After their formation autophagosomes fuse with lysosomes within which their inner membranes and the contents are degraded. Autophagy has the ability to selectively capture and subsequently degrade aggregated and ubiquitinated proteins. This is mediated by the p62 cargo receptor, which is required for the aggregation of these proteins into larger structures. These structures then serve as templates for autophagosome formation. I will present our results from a fully reconstituted system, which enabled us to dissect the interplay between p62 and ubiquitin positive proteins during protein aggregation in selective autophagy.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Some recent contributions to the modeling of the polymerization and depolymerization of actin filaments will be reviewed. Some results of the embedding of these models into the Filament Based Lamellipodium Model will be presented.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Mathematical modelling of protein polymerisation is a challenging topic, with wide applications, from actin filaments in myocytes (muscle tissues) to the so-called amyloid diseases (e.g. Alzheimer's, Parkinson's or Creuzfeldt-Jakob's diseases). In this talk, we will give an overview of recent results for both deterministic - where statistical mechanical fluctuations arising from intrinsic noise are negligible - and stochastic approaches, envisaged as giving complementary insights on the still largely mysterious intrinsic mechanisms of polymerisation. A data assimilation approach is developed in parallel of more specific methods for fragmentation estimation. The results we will present are partly joint work with A. Armiento, J. Calvo, S. Eugène, M. Escobedo, P. Moireau, B. Perthame, H. Rezaei, P. Robert, M. Tournus and W.F. Xue.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Reine1, Charles-Adrien Richard1, Tina Knäpple1 Vincent Béringue1* and Human Rezaei1* 1: INRA, UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas 78350, France *: Corresponding authors The prion phenomenon is based on autonomous structural information propagation towards single or multiple protein conformation changes. During this last decade the prion concept referring the transmission of structural information has been extended to several regulation systems and pathologies including Alzheimer and Parkinson’s diseases. Despite intensive investigation, the molecular basis of structural information transmission remains obscure. Templating (i.e. secondary nucleation as vector of structural information) has been proposed as origin of autocatalytic structural information perpetuation. However, the templating process does not consider the spreading process which consists in an exponential amplification of structural information. Active fibril fragmentation (AFF) constitutes a solution for exponential spreading and amplification of the structural information as strongly suggested in fungi prions (Shorter and Lindquist, Mol Cell, 2006). In the present work, we demonstrate that mammalian Prion assemblies (PrPSc) are constituted from an oligomeric elementary brick called suPrP. We show that in physiological conditions Prion assemblies are in equilibrium with suPrP. The existence of such equilibrium as simple depolymerization/condensation process is sufficient to spread the replicative unit through the release of suPrP, followed by its Brownian diffusion and condensation into PrPSc and discards the requirement of fragmentation for prion spreading.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

We investigate the oscillatory behaviour of the PrP protein during the polymerization/depolymerization process. In order to modelize this oscillatory process, we study a simplified Belousov-Zhabotinsky reaction from a kinetic point of view. This simplified oscillatory system of chemical reactions allows us to introduce a modified Becker-Döring system where the trajectories oscillate. A key to have a closed oscillatory polymerization/depolymerization system is to consider different specices of polymers and monomers. We finally present several system where the numerical simulations show a more or less sustained oscillatory behaviour.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Nicola Vettore and Alexander K. Buell, Institute of Physical Biology, University of Düsseldorf Amyloid fibrils are thermodynamically very stable [1], but the origin of their enhanced stability with respect to the native state has not yet been elucidated in molecular detail. The high stabilities of amyloid fibrils render the study of their equilibrium behaviour challenging. One way to approach this issue, in direct analogy to the study of protein folding equilibria is denaturation with commonly used denaturants, such as GdmCl or Urea. A theoretical framework to extract from such measurements the free energy difference between the fibril state and the soluble state, based on Oosawa's linear polymerisation model, was proposed in [2]. Here we present experimental results of amyloid fibril equilibrium denaturation measured via capillary fluorescence over a wide range of temperatures. The data highlight how the influence of temperature seems of primary importance not only for the kinetics of fibril formation, but also for the thermodynamic stability of the fibrillar structures. We will also present our attempts to describe the temperature-dependence of fibril stability within a general thermodynamic framework. [1] A. J. Baldwin, T. P. J. Knowles, G. G. Tartaglia, A. W. Fitzpatrick, G. L. Devlin, S. L. Shammas, C. A. Waudby, M. F. Mossuto, S. Meehan, S. L. Gras, J. Christodoulou, S. J. Anthony-Cahill, P. D. Barker, M. Vendruscolo, and C. M. Dobson, J. Am. Chem. Soc. 133, 14160 (2011). [2] T. Narimoto, K. Sakurai, A. Okamoto, E. Chatani, M. Hoshino, K. Hasegawa, H. Naiki, and Y. Goto, FEBS Lett. 576, 313 (2004).

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

A number of devastating human disorders, for example Alzheimer's disease (AD), Hungtington's diseases, type 2 diabetes and transmissible spongiform encephalopathies (TSEs), are associated with the abnormal folding and assembly of proteins. The net result of this misfolding is the formation of large insoluble protein deposits and small toxic and transmissible protein particles in a state called amyloid. What are the molecular mechanisms that govern the amyloid fibrils’ potential to seed the formation of new aggregates, to propagate the amyloid state as prion particles, and to damage cells in amyloid-associated diseases? We have developed AFM imaging approaches that are capable of resolving the fibril particle concentrations, their length distributions, as well as their toxic and infective potential to cells. With these approaches, we have shown that the disease-associated properties of amyloid can be linked to small nano-sized amyloid particles created through the breakage of amyloid fibrils. The approaches we have developed offer new opportunities to determine, quantify, and predict the course and the consequences in amyloid assembly of cytotoxic, infectious as well as functional amyloid systems.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

We consider the pure fragmentation fragmentation equation and address the question of estimating the fragmentation parameters (division rate and fragmentation kernel) from measurements of the size distribution at various times. Under the assumption of a polynomial division rate and a self-similar fragmentation kernel, we use the well-known asymptotic behaviour of the solution to guarantee the well-posedness of our inverse problem and provide a representation formula for the fragmentation kernel. The tools used are the Mellin transform and the Wiener-Hopf method. Motivations for studying this problem and applications to amyloid fibril breakage will be described in the talk of W.F. Xue.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Guillaume van der Rest, Human, Rezaei, Frédéric Halgand, Université Paris Sud, Laboratoire de Chimie Physique Prion protein is involved in deadly neurodegenerative diseases. Its pathogenicity is linked to its structural conversion (a-helix to b-strand transition). However, recent studies suggest that prion protein can follow a plurality of conversion pathways which hints towards different conformers that might coexist in solution. We therefore decided to screen the ovine and human PrP monomers using ion mobility coupled to mass spectrometry following electrospray ionization. After a short presentation of ion mobility for studying ionized proteins in the gas phase, we will briefly discuss issues with the collision cross section calibration procedure that we have encountered when using travelling wave ion mobility. We will also discuss the development of an automated data extraction pipeline for which we developed a Python/Qt script base interface. Infusion of monomeric PrP solutions have shown that at least three PrP conformers are observed in the gas phase. PrP monomers are known to lead to the formation of oligomeric species in specific conditions (temperature, pH and buffer), which are not compatible with mass spectrometry. We have therefore developed a size-exclusion chromatography IMS-MS setup with the aim to study the oligomers produced in these conditions. The development of this SEC-IMS-MS methodology will be presented as well as its application for calibration with standard protein complexes. Although we did not achieve resolution of the large (O1 ~36-mer) oligomeric species, optimization of the experimental parameters led to the observation of the small (O3) oligomeric species. One key observation in this process was that the abundance of the gas phase monomeric conformers changed upon the oligomerization process. First results allow us to interpret this as an effect of monomer concentration on the ratio of conformers present in solution, which is observed only in specific buffer conditions.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Yi Yin*, 1, Stéphanie Prigent1, Joan Torrent, Dirk Drasdo1, Human Rezaei, and Marie Doumic1 1. INRIA Paris, and Sorbonne Universités UPMC Univ. Paris 6, Laboratoire Jacques-Louis Lions, Paris, France, * yi.yin@inria.fr Protein aggregation into fibrils is a key process in amyloid diseases and also in other biological processes. The quantification of fibrils’ morphology and molecular structures is urgently needed in understanding of the key mechanisms and properties of fibrils. In this study, we propose an automated image analysis procedure to extract and quantify fibril morphological features from transmission electron microscopy (TEM) images. Fibrils are segmented by a ‘maximum entropy’ thresholding method and then the ‘fast marching’ skeletonization is applied to detect the fibril centerlines. The individual information of each fibril is gathered based on the fibril segmentation and extracted centerline, including the length (following the curvature of the fibrils, which are rarely straight lines), the varying width along the length, the curvature, as well as the number, position and length of branches. The intricate overlapping and branching structures are identified based on the angles between fibril segments. The proposed method was tested on experiments on the prion protein (PrP), which also allows us to explain in detail the parameters needed for the image analysis. Our method has high estimation accuracy (e.g. width estimation as shown in the figure). The results from different mutants of the PrP protein fibrils showed the potential of the method in fibrils classification through a statistical analysis. Romain

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

In this talk I will discuss various aspects of the kinetics and thermodynamics of the self assembly of peptides into amyloid fibrils and crystals. I will present a theoretical framework that allows to determine free energy barriers and entropies from kinetic data of amyloid fibril growth [1,2]. I will contrast the kinetic behaviour of longer, amyloid forming sequences with that of aromatic dipeptides that form crystals, rather than amyloid fibrils [3,4]. Furthermore, I will present the phenomenon of autocatalytic secondary nucleation, whereby new amyloid fibrils nucleate on the surface of existing ones [5,6]. In particular, I will show how this phenomenon manifests itself in kinetic measurements of protein aggregation, and how biosensing can be used to explore its molecular origin [6,7]. [1] A. K. Buell, J. R. Blundell, C. M. Dobson, M. E. Welland, E. M. Terentjev, and T. P. Knowles, Phys. Rev. Lett. 104, 228101 (2010). [2] A. K. Buell, A. Dhulesia, D. A. White, T. P. J. Knowles, C. M. Dobson, and M. E. Welland, Angew. Chem. Int. Ed Engl. 51, 5247 (2012). [3] T. O. Mason, T. C. T. Michaels, A. Levin, E. Gazit, C. M. Dobson, A. K. Buell, and T. P. J. Knowles, J. Am. Chem. Soc. 138, 9589 (2016). [4] T. O. Mason, A. Levin, C. M. Dobson, E. Gazit, T. P.J. Knowles and A. K. Buell, JACS under revision, (n.d.). [5] A. K. Buell, C. Galvagnion, R. Gaspar, E. Sparr, M. Vendruscolo, T. P. J. Knowles, S. Linse, and C. M. Dobson, Proc. Natl. Acad. Sci. 111, 7671 (2014). [6] R. Gaspar, G. Meisl, A. K. Buell, L. Young, C. F. Kaminski, T. P. J. Knowles, E. Sparr, and S. Linse, Q. Rev. Biophys. 50, (2017). [7] A. Šariæ, A. K. Buell, G. Meisl, T. C. T. Michaels, C. M. Dobson, S. Linse, T. P. J. Knowles, and D. Frenkel, Nat. Phys. 12, 874 (2016).

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

We present a new model for multi-agent dynamics where each agent is described by its position and body attitude: agents travel at a constant speed in a given direction and their body can rotate around it adopting different configurations. Agents try to coordinate their body attitudes with the ones of their neighbours. This model is inspired by the Vicsek model. The goal of this talk will be to present this new flocking model, its relevance and the derivation of the macroscopic equations from the particle dynamics. In collaboration with Pierre Degond (Imperial College London) and Amic Frouvelle (Université Paris Dauphine).

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)

Davy Martin1, Joan Torrent i Mas1, Stéphanie Prigent1, Mathieu Mezache2, Marie Doumic-Jauffret2, Vincent Béringue1 and Human Rezaei1* 1. National Institute for Agricultural Research (INRA), Pathological Macro-assemblies and Prion Pathology group (MAP2), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, 78350-F, France 2. Sorbonne Universités, Inria, UPMC Univ Paris 06, Lab. J.L. Lions UMR CNRS 7598, Paris, France The prion phenomenon is based on autonomous structural information propagation towards single or multiple protein conformational changes. Since this last decade the prion concept referring to the transmission of structural information has been extended to several regulation systems and pathologies including Alzheimer and Parkinson’s diseases. The unified theory in Prion replication implies structural information transference (SIT) from the prion to a non-prion conformer through a mechanism also called improperly, with regards to biophysical considerations “seeding” phenomenon. Therefore considering prion replication as a structural information transduction from a donor (i.e. template) to an acceptor (i.e. substrate) through a transduction interface a new questioning arises: what are molecular mechanisms of the auto-perpetuation of the Prion structural information and its faithfulness? Considering the Prion propagation as more or less faithful perpetuation of structural information, in the present work, we explored the concept of prion quasi-species (i.e. existence of prion heterogeneous assemblies) and highlighted the existence of prion network, which has an autopoietic behaviour (autoreplicative). Our observations strongly suggest that specific criteria in term of: protein structure, delayprocess and thermo-kinetics should be collated before a system become dissipative and autopoietic.

• Thematic program: Models in Biology and Medicine (2016/2017)
• Event: Workshop on "Protein Aggregation: Biophysics and Mathematics" (2017)