检索结果-内蒙古大学图书馆

Mechanically-driven growth and competition in a Voronoi model of tissues

学校读者我要写书评

暂无评论

arXiv 2024年

作者： Brézin, Louis Korolev, Kirill S. Department of Physics Graduate Program in Bioinformatics Biological Design Center Boston University BostonMA02215 United States

The mechanisms leading cells to acquire a fitness advantage and establish themselves in a population are paramount to understanding the development and growth of cancer. Although there are many works that study separately either the evolutionary dynamics or the mechanics of cancer, little has been done to couple evolutionary dynamics to mechanics. To address this question, we study a confluent model of tissue using a Self-Propelled Voronoi (SPV) model with stochastic growth rates that depend on the mechanical variables of the system. The SPV model is an out-of-equilibrium model of tissue derived from an energy functional that has a jamming/unjamming transition between solid-like and liquid-like states. By considering several scenarios of mutants invading a resident population in both phases, we determine the range of parameters that confer a fitness advantage and show that the preferred area and perimeter are the most relevant ones. We find that the liquid-like state is more resistant to invasion and show that the outcome of the competition can be determined from the simulation of a non-growing mixture. Moreover, a mean-field approximation can accurately predict the fate of a mutation affecting mechanical properties of a cell. Our results can be used to infer evolutionary dynamics from tissue images, understand cancer-suppressing effects of tissue mechanics, and even search for mechanics-based therapies. © 2024, CC BY.

关键词： Tissue

New sector morphologies emerge from anisotropic colony growth

学校读者我要写书评

暂无评论

arXiv 2024年

作者： Swartz, Daniel W. Lee, Hyunseok Kardar, Mehran Korolev, Kirill S. Department of Physics Massachusetts Institute of Technology CambridgeMA02139 United States Department of Physics Graduate Program in Bioinformatics and Biological Design Center Boston University BostonMA02215 United States

Competition during range expansions is of great interest from both practical and theoretical view points. Experimentally, range expansions are often studied in homogeneous Petri dishes, which lack spatial anisotropy that might be present in realistic populations. Here, we analyze a model of anisotropic growth, based on coupled Kardar-Parisi-Zhang and Fisher-Kolmogorov-Petrovsky-Piskunov equations that describe surface growth and lateral competition. Compared to a previous study of isotropic growth, anisotropy relaxes a constraint between parameters of the model. We completely characterize spatial patterns and invasion velocities in this generalized model. In particular, we find that strong anisotropy results in a distinct morphology of spatial invasion with a kink in the displaced strain ahead of the boundary between the strains. This morphology of the out-competed strain is similar to a shock wave and serves as a signature of anisotropic growth. Copyright © 2024, The Authors. All rights reserved.

关键词： Strain

Competition on the edge of an expanding population

学校读者我要写书评

暂无评论

arXiv 2023年

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. Copyright © 2023, The Authors. All rights reserved.

关键词：

Computational design of serine hydrolases

学校读者我要写书评

暂无评论

Science (New York, N.Y.) 2025年第6744期388卷 eadu2454页

作者： Lauko, Anna Pellock, Samuel J. Sumida, Kiera H. Anishchenko, Ivan Juergens, David Ahern, Woody Jeung, Jihun Shida, Alexander F. Hunt, Andrew Kalvet, Indrek Norn, Christoffer Humphreys, Ian R. Jamieson, Cooper Krishna, Rohith Kipnis, Yakov Kang, Alex Brackenbrough, Evans Bera, Asim K. Sankaran, Banumathi Houk, K.N. Baker, David Department of Biochemistry University of Washington Seattle WA United States Institute for Protein Design University of Washington Seattle WA United States Graduate Program in Biological Physics Structure and Design University of Washington Seattle WA United States Department of Chemistry University of Washington Seattle WA United States Graduate Program in Molecular Engineering University of Washington Seattle WA United States Paul G. Allen School of Computer Science and Engineering University of Washington Seattle WA United States Medical Scientist Training Program University of Washington Seattle WA United States Howard Hughes Medical Institute University of Washington Seattle WA United States Department of Chemistry and Biochemistry University of California Los Angeles CA United States

The design of enzymes with complex active sites that mediate multistep reactions remains an outstanding challenge. With serine hydrolases as a model system, we combined the generative capabilities of RFdiffusion with an ensemble generation method for assessing active site preorganization at each step in the reaction to design enzymes starting from minimal active site descriptions. Experimental characterization revealed catalytic efficiencies (kcat/Km) up to 2.2 × 105 M-1 s-1 and crystal structures that closely match the design models (Cα root mean square deviations <1 angstrom). Selection for structural compatibility across the reaction coordinate enabled identification of new catalysts remove with five different folds distinct from those of natural serine hydrolases. Our de novo approach provides insight into the geometric basis of catalysis and a roadmap for designing enzymes that catalyze multistep transformations.

关键词：

Correction to: Multistate and functional protein design using RoseTTAFold sequence space diffusion (Nature Biotechnology, (2024), 10.1038/s41587-024-02395-w)

学校读者我要写书评

暂无评论

Nature Biotechnology 2024年

作者： Lisanza, Sidney Lyayuga Gershon, Jacob Merle Tipps, Samuel W. K. Sims, Jeremiah Nelson Arnoldt, Lucas Hendel, Samuel J. Simma, Miriam K. Liu, Ge Yase, Muna Wu, Hongwei Tharp, Claire D. Li, Xinting Kang, Alex Brackenbrough, Evans Bera, Asim K. Gerben, Stacey Wittmann, Bruce J. McShan, Andrew C. Baker, David Department of Biochemistry University of Washington SeattleWA United States Institute for Protein Design University of Washington SeattleWA United States Graduate Program in Biological Physics Structure and Design University of Washington SeattleWA United States Department of Molecular Engineering University of Washington SeattleWA United States Molecular & amp Cellular Biology Medical Scientist Training Program University of Washington SeattleWA United States Faculty of Engineering Sciences Heidelberg University Heidelberg Germany School of Chemistry and Biochemistry Georgia Institute of Technology AtlantaGA United States Office of the Chief Scientific Officer Microsoft RedmondWA United States Howard Hughes Medical Institute University of Washington SeattleWA United States

Correction to: Nature Biotechnologyhttps://***/10.1038/s41587-024-02395-w, published online 25 September 2024. In the version of the article initially published, in the key to Fig. 2f the colors were swapped and have now been amended so that "W guidance" is purple and "Unconditional" is grey. In Fig. 5a, the color of "Child B" has been corrected from pink to purple, and in Fig. 5d, "β-helix" has now been amended to "β-sheet". These corrections have been made to the HTML and PDF versions of the article. © The Author(s) 2024.

关键词：

Mini Light-Emitting Diode Technology with High Quantum Efficient NIR-II Partially Inverse Spinel MgGa2O4:Cr3+,Ni2+ Nanophosphors

学校读者我要写书评

暂无评论

Advanced Optical Materials 2024年第19期12卷

作者： Satpathy, Aishwarya Huang, Wen-Tse Liu, Tzu-Hsuan Su, Ting-Yi Zhang, Wei Kamiński, Mikolaj Grzegorczyk, Maciej Chen, Jia-Hao Cherng, Ding-Hua Lu, Kuang-Mao Chen, Xueyuan Mahlik, Sebastian Liu, Ru-Shi Department of Chemistry National Taiwan University Taipei106 Taiwan Fujian Key Laboratory of Nanomaterials and CAS Key Laboratory of Design and Assembly of Functional Nanostructures Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fujian Fuzhou350002 China Nanoscience and Technology Program Taiwan International Graduate Program Academia Sinica and National Taiwan University Academia Road 128 Taipei Nankang115 Taiwan Institute of Experimental Physics Faculty of Mathematics Physics and Informatics University of Gdańsk Wita Stwosza 57 Gdańsk80–308 Poland Everlight Electronics Co. Ltd. New Taipei City238 Taiwan International Centre for Theory of Quantum Technologies University of Gdańsk Gdańsk80–308 Poland

The increasing demand for second near-infrared (NIR-II) region materials, which retain the advantage of minimal scattering and immense applications in the medical and NIR spectroscopy field, has led to considerable research in this region. A mini light-emitting diode (mini-LED) is essential for backlighting liquid crystal displays, indicating the need for the small size of phosphors. However, current market phosphors must be more significant to be a viable option for mini-LEDs. This scenario necessitates the synthesis of small-sized phosphors to be used in mini-LEDs. In this work, a mesoporous silica nanoparticle (MSN) and incorporated the Mg1−yGa2−xO4:xCr3+,yNi2+ system is fabricated. The structural investigation confirmed the single phase of MgGa2O4 with a pore size of 2.73 nm for the MSN. The results showed a steady NIR-II signal at 1270 nm and an enhanced energy transfer with a high quantum yield of 79.2% for a nanophosphor. The mini-LED package revealed a 1000–1600 nm signal, qualifying the nanophosphor for realistic applications. This work can make provisions for various NIR-II nanophosphors in the LED industry. © 2024 Wiley-VCH GmbH.

关键词： Energy transfer

1 Slow expanders invade by forming dented fronts in microbial 2 colonies

学校读者我要写书评

暂无评论

arXiv 2021年

作者： Lee, Hyunseok Gore, Jeff Korolev, Kirill S. Physics of Living Systems Group Department of Physics Massachusetts Institute of Technology CambridgeMA02139 United States Department of Physics Graduate Program in Bioinformatics Biological Design Center Boston University BostonMA02215 United States

Most organisms grow in space, whether they are viruses spreading within a host tissue or invasive species colonizing a new continent. Evolution typically selects for higher expansion rates during spatial growth, but it has been suggested that slower expanders can take over under certain conditions. Here, we report an experimental observation of such population dynamics. We demonstrate that the slower mutants win not only when the two types are intermixed at the front but also when they are spatially segregated into sectors. The latter was thought to be impossible because previous studies focused exclusively on the global competitions mediated by expansion velocities but overlooked the local competitions at sector boundaries. We developed a theory of sector geometry that accounts for both local and global competitions and describes all possible sector shapes. In particular, the theory predicted that a slower, but more competitive, mutant forms a dented V-shaped sector as it takes over the expansion front. Such sectors were indeed observed experimentally and their shapes matched up quantitatively with the theory. In simulations, we further explored several mechanism that could provide slow expanders with a local competitive advantage and showed that they are all well-described by our theory. Taken together, our results shed light on previously unexplored outcomes of spatial competition and establish a universal framework to understand evolutionary and ecological dynamics in expanding populations. © 2021, CC BY-NC-ND.

关键词： Competition

BPS2025 - Structural and functional characterization of integrin α5-targeting antibodies for anti-angiogenic therapy

学校读者我要写书评

暂无评论

Biophysical Journal 2025年第3期124卷 12a-12a页

作者： Adam Nguyen Joel B. Heim Gabriele Cordara Matthew C. Chan Hedda Johannesen Cristine Charlesworth Ming Li Caleigh M. Azumaya Benjamin Madden Ute Krengel Alexander Meves Melody G. Campbell Basic Sciences Fred Hutchinson Cancer Center Seattle WA USA Biological Physics Structure and Design Graduate Program University of Washington Seattle WA USA Department of Dermatology Mayo Clinic Rochester MN USA Department of Chemistry University of Oslo Oslo Norway Medical Genome and Proteomics Core Mayo Clinic Rochester MN USA

An HIV-1 broadly neutralizing antibody overcomes structural and dynamic variation through highly focused epitope targeting

学校读者我要写书评

暂无评论

Npj viruses 2023年第1期1卷 2页

作者： Edgar A Hodge Ananya Chatterjee Chengbo Chen Gajendra S Naika Mint Laohajaratsang Vidya Mangala Prasad Kelly K Lee Department of Medicinal Chemistry University of Washington Seattle WA 98195 USA. Molecular Biophysics Unit Indian Institute of Science Bangalore Karnataka 560012 India. Biological Physics Structure and Design Graduate Program University of Washington Seattle WA 98195 USA. Center for Infectious Diseases Research Indian Institute of Science Bangalore Karnataka 560012 India.

The existence of broadly cross-reactive antibodies that can neutralize diverse HIV-1 isolates (bnAbs) has been appreciated for more than a decade. Many high-resolution structures of bnAbs, typically with one or two well-characterized HIV-1 Env glycoprotein trimers, have been reported. However, an understanding of how such antibodies grapple with variability in their antigenic targets across diverse viral isolates has remained elusive. To achieve such an understanding requires first characterizing the extent of structural and antigenic variation embodied in Env, and then identifying how a bnAb overcomes that variation at a structural level. Here, using hydrogen/deuterium-exchange mass spectrometry (HDX-MS) and quantitative measurements of antibody binding kinetics, we show that variation in structural ordering in the V1/V2 apex of Env across a globally representative panel of HIV-1 isolates has a marked effect on antibody association rates and affinities. We also report cryo-EM reconstructions of the apex-targeting PGT145 bnAb bound to two divergent Env that exhibit different degrees of structural dynamics throughout the trimer structures. Parallel HDX-MS experiments demonstrate that PGT145 bnAb has an exquisitely focused footprint at the trimer apex where binding did not yield allosteric changes throughout the rest of the structure. These results demonstrate that structural dynamics are a cryptic determinant of antigenicity, and mature antibodies that have achieved breadth and potency in some cases are able to achieve their broad cross-reactivity by "threading the needle" and binding in a highly focused fashion, thus evading and overcoming the variable properties found in Env from divergent isolates.

关键词： Biochemistry Immunology Microbiology