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SUMMARY:CECAM workshop: “Liquid\, soft\, alive: Identifying the biologic
 al questions in the physics cells”
DTSTART:20230213T140000
DTEND:20230216T130000
DTSTAMP:20260407T024744Z
UID:af98488d1619ed2c014c5be298bb3f157471cff9f18cc22913402886
CATEGORIES:Conferences - Seminars
DESCRIPTION:You can apply to participate and find all the relevant informa
 tion (speakers\, abstracts\, program\,...) on the event website: www.ceca
 m.org/workshop-details/1129\n\nDESCRIPTION:\nDuring the past decade there 
 has been a  shift  in  the  way  equilibrium  con- cepts in soft mat
 ter and statistical physics have been employed to understand diverse probl
 ems in biology based on liquid-liquid phase separation (LLPS)\, macromolec
 ular crowding\, or formation of equilibrium clusters and aggregates (conde
 nsates). A common aspect of all such processes is the likely existence of 
 phase diagrams with multiple stable or metastable polymorphic disordered l
 iq- uid states [1]. However\, unlike the passive phase behaviour that is o
 bserved in natural and man-made phase separation processes (well understoo
 d since long ago)\, cellular LLPS processes at work in living systems are 
 intrinsically non- equilibrium as a result of the intricate array of inter
 nal and external chemostats and mass/charge currents. On the one hand\, un
 derstanding the fundamental mechanism of such non-equilibrium phase separa
 tion is crucial for better under- standing the functioning (and malfunctio
 ning) of the cell. On the other hand\, the better the inner workings of th
 e cell are understood at a fundamental level\, the more researchers can ge
 t inspiration for creating soft matter physics analogs pointing to new str
 ategies for novel functional materials design.\nThis workshop aims at esta
 blishing an environment for fertile cross-talk be- tween cell biologists a
 nd soft-matter physicists [2] who are interested to run experiments and mo
 del the non-equilibrium processes that govern key cellular processes. The 
 primary deliverable of such cross-fertilization will be to clearly identif
 y the main biological questions for physicists to address.  The second st
 rong objective of the proposed workshop is to discuss state-of-the-art com
 - putational approaches bridging length- and time-scales to study these co
 mplex soft matter and bio-molecular systems.\n\nLiquid-liquid phase separa
 tion in biology\nThe living cells are organized in a highly compartmentali
 zed fashion. Besides membrane-bound organelles\, such as lysosomes and mit
 ochondria\, there is a plethora of membraneless structures formed through 
 liquid-liquid phase separa- tion (LLPS) act as dynamical cellular organell
 es [3]. Many aggregation-related processes conducive to neurodegenerative 
 diseases could be regarded and better understood as LLPS-driven mechanisms
  [4]. Moreover\, some vital regulative processes and kinetic mechanisms in
  cell biology\,  such as RNA-based regula- tion of gene expression and ce
 rtain enzymatic kinetics\, could be viewed anew as epiphenomena of LLPS-mo
 dulated activity. Consequently\, during the past decade\, there has been a
 n explosive growth in the study of controlled\, nano-scale liquid-liquid p
 hase separation (LLPS) inside living cells. It should be stressed that\, u
 nlike the passive LLPS that takes place in many man-made separation proces
 ses\, cellular LLPS is intrinsically non-equilibrium and strongly confined
  (e.g.\, in the cell nucleus).   The vigorous research activity – invo
 lving biolo- gists\, chemists and physicists – is revolving around the c
 entral question on how complex dynamic environment can organize and contro
 l multiple (bio)chemical processes in parallel. Understanding the function
 ing of such complex micro- reactors is also intimately connected with form
 ation of the protocells [5].  The role of LLPS in basic processes at the 
 core of life has contributed to bringing soft matter physics closer to fun
 damental questions that arise in cell biology and prebiotic chemistry.\n\n
 Macromolecular crowding\nThe cell is a nanoporous\, active\, viscoelastic\
 , compartmentalized open reac- tor [6]. Many molecular species\, whose siz
 es span two to three orders of mag- nitude\, diffuse passively or are acti
 vely transported from one place to another. However\, the available space 
 for mass transport across the cell is small: up to 40 % of the overall vol
 ume is occupied by biomolecules\, complexes\, organelles or cytoskeletal s
 tructures [7]. Collectively\, this condition is referred to in the litera-
  ture as macromolecular crowding (MC) [8]. Although rooted in excluded-v
 olume effects\, researchers have long realized that the role played by MC 
 is subtle and indissolubly connected to other closely related facets of cr
 owded places. For ex- ample\, while excluded-volume effects obviously may 
 exert entropic forces that could stabilize polymers such as proteins withi
 n the cell\, the presence of modest anisotropic weak non-specific (i.e. oc
 curring among non-specific portions of the partners’ surfaces) interacti
 ons may have the opposite effect\, namely lead to a destabilization of t
 he folded conformation [9]. Moreover\, crucial kinetic processes such as e
 nzymatic catalysis\, turned out to be influenced by volume exclusion and
  related accompanying factors\, such as non-specific interactions [10] an
 d space segmentation [11\, 12] (not only it is important how much space 
 is available\, but also how that is structured).\n\nClusters\, aggregate
 s\, protocells\nBiomacromolecules can aggregate to form clusters and netwo
 rks in various ways [13]– with broad biological implications. A wide var
 iety of proteins form fibrillar aggregates (amyloids)\, which are implicat
 ed in a number of human diseases [14]: Alzheimer’s\, Creutzfeldt-Jakob a
 nd Huntingdon’s diseases (in the brain)\, Parkinson’s disease (in nerv
 e cells)\, type-II diabetes (in the pancreas) [15]\, and also autoimmune d
 isorders [16]. Assemblies of protein capsids are vital for functioning of 
 viruses and packing of genetic materials. Coacervates are clusters or drop
 lets (the distinction is sometimes unclear\, experimentally [17]) that are
  formed due to a combination of electrostatic interactions between poly- e
 lectrolytes and hydrophobic interactions. The formation of such microscopi
 c clusters in relatively dilute solutions seems to be crucial for origin o
 f life models – in this context they are called protocells [18\, 19].\nA
 ggregation of biomolecules is a complex problem that lends itself well to 
 soft matter studies.   Visualization of dynamic biomolecular clusters is
  challenging and techinques such as small-angle neutron scattering [13]\, 
 NMR [20]\, neutron spin echo [21]\, or similar have to be used. Elucidatin
 g mechanisms of clus- ter formation is thus much easier in colloidal model
  systems where qualitative insights can be gleaned from direct optical tec
 hniques [22] coupled with multi- scale simulations [23]. A general prerequ
 isite for aggregation is some form of inter-particle attraction\, generate
 d by  physical (e.g.\,  van der  Waals or deple- tion interactions)\, o
 r chemical means. The aggregation process can be diffusion limited (in the
  absence of a repulsive barrier)\, or reaction-limited [24] (with a barrie
 r). Depending on the interaction profile\, aggregation can therefore eithe
 r be irreversible (slowly growing static clusters) or thermodynamic and re
 versible (dynamic [21] clusters). The size and structure of the aggregates
  are delicately connected to their biological function: disordered medium-
 sized aggregates of proteins are usually toxic – unlike individual prote
 ins\, or their large native (or- dered) aggregates. A recent review [14] s
 uggests that the  toxicity  is  related either to their larger diffusiv
 ity\, or higher degree of hydrophobicity. Another study [16] reports that 
 the size and geometry of the crystalline clusters of an- timicrobial pepti
 des crucially affect the activation of immune receptors and that multivale
 nt binding [25] plays an important role in understanding such effects.\n\n
 Soft and bio-inspired materials\nBiological systems can achieve remarkable
  efficiency and selectivity\,  but thus far\, the concept of driven LLPS 
 has barely been exploited in man-made devices\, and protein aggregation re
 mains a challenge for drug formulations. Better un- derstanding of the int
 erplay between equilibrium thermodynamic driving forces and non-equilibriu
 m activity can open new strategies to design biomimetic sep- aration proce
 sses and new materials utilizing such mechanisms.
LOCATION:BCH 2103 https://plan.epfl.ch/?room==BCH%202103
STATUS:CONFIRMED
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