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Article ; Online: Specialization at an expanding front.

Li, Lauren H / Kardar, Mehran

2023 Volume 108, Issue 3, Page(s) L032402

Abstract: As a population grows, spreading to new environments may favor specialization. In this paper, we introduce and explore a model for specialization at the front of a colony expanding synchronously into new territory. We show through numerical simulations ... ...

Abstract	As a population grows, spreading to new environments may favor specialization. In this paper, we introduce and explore a model for specialization at the front of a colony expanding synchronously into new territory. We show through numerical simulations that, by gaining fitness through accumulating mutations, progeny of the initial seed population can differentiate into distinct specialists. With competition and selection limited to the growth front, the emerging specialists first segregate into sectors, which then expand to dominate the entire population. We quantify the scaling of the fixation time with the size of the population and observe different behaviors corresponding to distinct universality classes: unbounded and bounded gains in fitness lead to superdiffusive (z=3/2) and diffusive (z=2) stochastic wanderings of the sector boundaries, respectively.
Language	English
Publishing date	2023-09-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.108.L032402
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Article ; Online: Scale-Dependent Heat Transport in Dissipative Media via Electromagnetic Fluctuations.

Krüger, Matthias / Asheichyk, Kiryl / Kardar, Mehran / Golestanian, Ramin

Physical review letters

2024 Volume 132, Issue 10, Page(s) 106903

Abstract: We develop a theory for heat transport via electromagnetic waves inside media, and use it to derive a spatially nonlocal thermal conductivity tensor, in terms of the electromagnetic Green's function and potential, for any given system. While typically ... ...

Abstract	We develop a theory for heat transport via electromagnetic waves inside media, and use it to derive a spatially nonlocal thermal conductivity tensor, in terms of the electromagnetic Green's function and potential, for any given system. While typically negligible for optically dense bulk media, the electromagnetic component of conductivity can be significant for optically dilute media, and shows regimes of Fourier transport as well as unhindered transport. Moreover, the electromagnetic contribution is relevant even for dense media, when in the presence of interfaces, as exemplified for the in-plane conductivity of a nanosheet, which shows a variety of phenomena, including absence of a Fourier regime.
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	208853-8
ISSN	1079-7114 ; 0031-9007
ISSN (online)	1079-7114
ISSN	0031-9007
DOI	10.1103/PhysRevLett.132.106903
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Book ; Online: Universal characterization of epitope immunodominance from a multi-scale model of clonal competition in germinal centers

Ferretti, Federica / Kardar, Mehran

2023

Abstract: We introduce a novel, multi-scale model for affinity maturation, which aims to capture the intra-clonal, inter-clonal and epitope-specific organization of the B cell population in a germinal center. We describe the evolution of the B cell population via ... ...

Abstract	We introduce a novel, multi-scale model for affinity maturation, which aims to capture the intra-clonal, inter-clonal and epitope-specific organization of the B cell population in a germinal center. We describe the evolution of the B cell population via a quasispecies dynamics, with species corresponding to unique B cell receptors (BCRs), where the desired multi-scale structure is reflected on the mutational connectivity of the accessible BCR space, and on the statistical properties of its fitness landscape. Within this mathematical framework, we study the competition among classes of BCRs targeting different antigen epitopes, and construct an effective \emph{immunogenic space} where epitope immunodominance relations can be universally characterized. We finally study how varying the relative composition of a mixture of antigens with variable and conserved domains allows for a parametric exploration of this space, and identify general principles for the rational design of two-antigen cocktails. Comment: 10 pages + 3 pages (appendix), 6 figures
Keywords	Quantitative Biology - Populations and Evolution ; Condensed Matter - Statistical Mechanics ; Physics - Biological Physics
Subject code	612
Publishing date	2023-10-16
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Active motion of passive asymmetric dumbbells in a non-equilibrium bath.

Belan, Sergey / Kardar, Mehran

The Journal of chemical physics

2021 Volume 154, Issue 2, Page(s) 24109

Abstract: Persistent motion of passive asymmetric bodies in non-equilibrium media has been experimentally observed in a variety of settings. However, fundamental constraints on the efficiency of such motion are not fully explored. Understanding such limits, and ... ...

Abstract	Persistent motion of passive asymmetric bodies in non-equilibrium media has been experimentally observed in a variety of settings. However, fundamental constraints on the efficiency of such motion are not fully explored. Understanding such limits, and ways to circumvent them, is important for efficient utilization of energy stored in agitated surroundings for purposes of taxis and transport. Here, we examine such issues in the context of erratic movements of a passive asymmetric dumbbell driven by non-equilibrium noise. For uncorrelated (white) noise, we find a (non-Boltzmann) joint probability distribution for the velocity and orientation, which indicates that the dumbbell preferentially moves along its symmetry axis. The dumbbell thus behaves as an Ornstein-Uhlenbeck walker, a prototype of active matter. Exploring the efficiency of this active motion, we show that in the over-damped limit, the persistence length l of the dumbbell is bound from above by half its mean size, while the propulsion speed v
Language	English
Publishing date	2021-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	3113-6
ISSN	1089-7690 ; 0021-9606
ISSN (online)	1089-7690
ISSN	0021-9606
DOI	10.1063/5.0030623
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Article ; Online: How persistent infection overcomes peripheral tolerance mechanisms to cause T cell-mediated autoimmune disease.

Yin, Rose / Melton, Samuel / Huseby, Eric S / Kardar, Mehran / Chakraborty, Arup K

Proceedings of the National Academy of Sciences of the United States of America

2024 Volume 121, Issue 11, Page(s) e2318599121

Abstract: T cells help orchestrate immune responses to pathogens, and their aberrant regulation can trigger autoimmunity. Recent studies highlight that a threshold number of T cells (a quorum) must be activated in a tissue to mount a functional immune response. ... ...

Abstract	T cells help orchestrate immune responses to pathogens, and their aberrant regulation can trigger autoimmunity. Recent studies highlight that a threshold number of T cells (a quorum) must be activated in a tissue to mount a functional immune response. These collective effects allow the T cell repertoire to respond to pathogens while suppressing autoimmunity due to circulating autoreactive T cells. Our computational studies show that increasing numbers of pathogenic peptides targeted by T cells during persistent or severe viral infections increase the probability of activating T cells that are weakly reactive to self-antigens (molecular mimicry). These T cells are easily re-activated by the self-antigens and contribute to exceeding the quorum threshold required to mount autoimmune responses. Rare peptides that activate many T cells are sampled more readily during severe/persistent infections than in acute infections, which amplifies these effects. Experiments in mice to test predictions from these mechanistic insights are suggested.
MeSH term(s)	Animals ; Mice ; Persistent Infection ; Peripheral Tolerance ; T-Lymphocytes ; Autoantigens ; Peptides ; Autoimmune Diseases
Chemical Substances	Autoantigens ; Peptides
Language	English
Publishing date	2024-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2318599121
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Article ; Online: Competition on the edge of an expanding population.

Swartz, Daniel W / Lee, Hyunseok / Kardar, Mehran / Korolev, Kirill S

ArXiv

2023

Abstract: In growing populations, the fate of mutations depends on their competitive ability against the ancestor and their ability to colonize new territory. Here we present a theory that integrates both aspects of mutant fitness by coupling the classic ... ...

Abstract	In growing populations, the fate of mutations depends on their competitive ability against the ancestor and their ability to colonize new territory. Here we present a theory that integrates both aspects of mutant fitness by coupling the classic description of one-dimensional competition (Fisher equation) to the minimal model of front shape (KPZ equation). We solved these equations and found three regimes, which are controlled solely by the expansion rates, solely by the competitive abilities, or by both. Collectively, our results provide a simple framework to study spatial competition.
Language	English
Publishing date	2023-01-18
Publishing country	United States
Document type	Preprint
ISSN	2331-8422
ISSN (online)	2331-8422
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Article ; Online: Interplay between morphology and competition in two-dimensional colony expansion.

Swartz, Daniel W / Lee, Hyunseok / Kardar, Mehran / Korolev, Kirill S

Physical review. E

2023 Volume 108, Issue 3, Page(s) L032301

Abstract	In growing populations, the fate of mutations depends on their competitive ability against the ancestor and their ability to colonize new territory. Here we present a theory that integrates both aspects of mutant fitness by coupling the classic description of one-dimensional competition (Fisher equation) to the minimal model of front shape (Kardar-Parisi-Zhang equation). We solve these equations and find three regimes, which are controlled solely by the expansion rates, solely by the competitive abilities, or by both. Collectively, our results provide a simple framework to study spatial competition.
MeSH term(s)	Mutation ; Genetic Fitness ; Genetics, Population
Language	English
Publishing date	2023-10-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.108.L032301
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Article ; Online: Polymer folding through active processes recreates features of genome organization.

Goychuk, Andriy / Kannan, Deepti / Chakraborty, Arup K / Kardar, Mehran

Proceedings of the National Academy of Sciences of the United States of America

2023 Volume 120, Issue 20, Page(s) e2221726120

Abstract: From proteins to chromosomes, polymers fold into specific conformations that control their biological function. Polymer folding has long been studied with equilibrium thermodynamics, yet intracellular organization and regulation involve energy-consuming, ...

Abstract	From proteins to chromosomes, polymers fold into specific conformations that control their biological function. Polymer folding has long been studied with equilibrium thermodynamics, yet intracellular organization and regulation involve energy-consuming, active processes. Signatures of activity have been measured in the context of chromatin motion, which shows spatial correlations and enhanced subdiffusion only in the presence of adenosine triphosphate. Moreover, chromatin motion varies with genomic coordinate, pointing toward a heterogeneous pattern of active processes along the sequence. How do such patterns of activity affect the conformation of a polymer such as chromatin? We address this question by combining analytical theory and simulations to study a polymer subjected to sequence-dependent correlated active forces. Our analysis shows that a local increase in activity (larger active forces) can cause the polymer backbone to bend and expand, while less active segments straighten out and condense. Our simulations further predict that modest activity differences can drive compartmentalization of the polymer consistent with the patterns observed in chromosome conformation capture experiments. Moreover, segments of the polymer that show correlated active (sub)diffusion attract each other through effective long-ranged harmonic interactions, whereas anticorrelations lead to effective repulsions. Thus, our theory offers nonequilibrium mechanisms for forming genomic compartments, which cannot be distinguished from affinity-based folding using structural data alone. As a first step toward exploring whether active mechanisms contribute to shaping genome conformations, we discuss a data-driven approach.
MeSH term(s)	Polymers/chemistry ; Chromatin/genetics ; Chromosomes/metabolism ; Genome ; Genomics
Chemical Substances	Polymers ; Chromatin
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2221726120
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Jg. 1995 - 2021: Lesesall (1.OG)
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Article ; Online: Inferring the intrinsic mutational fitness landscape of influenzalike evolving antigens from temporally ordered sequence data.

Doelger, Julia / Kardar, Mehran / Chakraborty, Arup K

Physical review. E

2022 Volume 105, Issue 2-1, Page(s) 24401

Abstract: There still are no effective long-term protective vaccines against viruses that continuously evolve under immune pressure such as seasonal influenza, which has caused, and can cause, devastating epidemics in the human population. To find such a broadly ... ...

Abstract	There still are no effective long-term protective vaccines against viruses that continuously evolve under immune pressure such as seasonal influenza, which has caused, and can cause, devastating epidemics in the human population. To find such a broadly protective immunization strategy, it is useful to know how easily the virus can escape via mutation from specific antibody responses. This information is encoded in the fitness landscape of the viral proteins (i.e., knowledge of the viral fitness as a function of sequence). Here we present a computational method to infer the intrinsic mutational fitness landscape of influenzalike evolving antigens from yearly sequence data. We test inference performance with computer-generated sequence data that are based on stochastic simulations mimicking basic features of immune-driven viral evolution. Although the numerically simulated model does create a phylogeny based on the allowed mutations, the inference scheme does not use this information. This provides a contrast to other methods that rely on reconstruction of phylogenetic trees. Our method just needs a sufficient number of samples over multiple years. With our method, we are able to infer single as well as pairwise mutational fitness effects from the simulated sequence time series for short antigenic proteins. Our fitness inference approach may have potential future use for the design of immunization protocols by identifying intrinsically vulnerable immune target combinations on antigens that evolve under immune-driven selection. In the future, this approach may be applied to influenza and other novel viruses such as SARS-CoV-2, which evolves and, like influenza, might continue to escape the natural and vaccine-mediated immune pressures.
Language	English
Publishing date	2022-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.105.024401
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Seascape origin of Richards growth.

Swartz, Daniel W / Ottino-Löffler, Bertrand / Kardar, Mehran

Physical review. E

2022 Volume 105, Issue 1-1, Page(s) 14417

Abstract: First proposed as an empirical rule over half a century ago, the Richards growth equation has been frequently invoked in population modeling and pandemic forecasting. Central to this model is the advent of a fractional exponent γ, typically fitted to the ...

Abstract	First proposed as an empirical rule over half a century ago, the Richards growth equation has been frequently invoked in population modeling and pandemic forecasting. Central to this model is the advent of a fractional exponent γ, typically fitted to the data. While various motivations for this nonanalytical form have been proposed, it is still considered foremost an empirical fitting procedure. Here, we find that Richards-like growth laws emerge naturally from generic analytical growth rules in a distributed population, upon inclusion of (i) migration (spatial diffusion) among different locales, and (ii) stochasticity in the growth rate, also known as "seascape noise." The latter leads to a wide (power law) distribution in local population number that, while smoothened through the former, can still result in a fractional growth law for the overall population. This justification of the Richards growth law thus provides a testable connection to the distribution of constituents of the population.
Language	English
Publishing date	2022-02-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2844562-4
ISSN	2470-0053 ; 2470-0045
ISSN (online)	2470-0053
ISSN	2470-0045
DOI	10.1103/PhysRevE.105.014417
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