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Physics of living systems

Understanding life through the physics of organization.

Cells are always changing. How do they keep working reliably? I study how membranes are built, moved and recycled, and how chromosomes are passed accurately to new cells.

Translucent cell and four molecular views of lipid transport, membrane turnover, vesicles and chromosome segregation
Yuji Sakai · Yokohama City UniversityTheory / Simulation / Experiment
The central question

From molecular interactions to the architecture of cells, physical principles connect biological function across scales.

Connecting principles

Stability and adaptability

How can biological structures remain reliable yet adapt, reorganize, and respond to change? Homeostasis and fidelity share this underlying challenge.

01

Robustness

Maintain function despite fluctuations

02

Plasticity

Reconfigure structure when needed

03

Self-organization

Create architecture from local interactions

04

Specificity

Act at the right place and time

02 / Research directions

From concepts to mechanisms

We combine simple physical models, computer simulations of moving molecules and experiments to study the same problem from different angles.

Select a research topic to read the background, scientific questions, research highlights and annotated publications.

03 / Scientific approach

Bridging scales. Finding principles.

My work began with theoretical physics and mathematical models of chromosome organization and membrane remodeling. I now combine molecular simulations with experimental studies to investigate the mechanisms behind these processes.

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01

Mathematical & physical modeling

Physical models help us explore how membranes bend, long DNA molecules fold, and proteins come together to build functional structures.

02

Molecular simulation

Molecular dynamics is a computer method for following how atoms or groups of atoms move. We use it to study changes in molecular shape, how molecules assemble and interact, and how forces at the molecular scale give rise to biological functions.

03

Integrated experimental validation

Imaging, structural biology and biochemical measurements help test predictions and connect molecular mechanisms to cellular function.

04 / Research in Motion

Research in Motion

From molecular interactions to cellular organization — simulations connected to individual research topics.

I / Homeostasis

Membrane Dynamics

TOPIC 02 / Lipid Transport

How Atg2 Transfers Lipids Between Membranes

A bridge-shaped Atg2 protein connects two membranes and allows lipids to move between them.

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TOPIC 03 / Membrane Turnover & Maturation

How Atg15 Extracts Lipids from Membranes

A membrane lipid is extracted toward the catalytic center of the Atg15 lipase.

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TOPIC 03 / Membrane Turnover & Maturation

How PI4P Facilitates STX17 Membrane Insertion

A molecular simulation illustrates STX17 transmembrane-segment insertion in a PI4P-containing membrane.

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II / Fidelity

Chromosome Dynamics

TOPIC 05 / Chromosome Shaping & Segregation

How Chromosomes Take Shape and Separate

A physical simulation of two chromosomes becoming organized and moving apart.

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TOPIC 06 / Mitotic Fidelity

How CCAN Complexes Assemble on DNA

Eight CCAN units are organized through DNA and four miniCENP-C dimers in a molecular simulation.

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05 / Tools & Computational Resources

Tools & Computational Resources

Computational methods and resources that connect physical models to biomolecular mechanisms.

01 / Molecular Dynamics

GENESIS

All-atom molecular dynamics of proteins, lipids and membranes.

02 / Coarse-Grained Simulation

Martini 3

Coarse-grained simulations to investigate larger molecular assemblies and membrane dynamics.

04 / High-Performance Computing

Fugaku

Large-scale biomolecular simulations on a high-performance computing platform.

06 / Selected publications

A research trajectory through recent papers

Eight recent publications from 2024–2026, spanning mathematical models, molecular mechanisms and cellular organization. Find more publications on the individual research pages.

2026
PNAS

Structural and mechanistic basis for membrane recognition and activation of the vacuolar lipase Atg15

Structural and functional analyses explain how a lipase recognizes a membrane and becomes active during breakdown.

Membrane curvature · lipid degradation
2026
bioRxiv · updated preprint

Atg1 phosphorylates Atg2 to gate phospholipid flow through a continuous conduit for autophagosome biogenesis

The preprint investigates how phosphorylation regulates the movement of lipids through a membrane-bridging protein.

Phosphorylation · lipid transfer
2026
bioRxiv · preprint

CCAN forms the spherical shell-like structure in interphase kinetochores

The preprint examines a shell-like higher-order arrangement of proteins that build the kinetochore.

Kinetochore architecture · multiscale simulation
2026
The EMBO Journal

Phosphorylation tunes p62 condensates to drive autophagic degradation of ubiquitinated proteins

Phosphorylation changes the properties of p62 condensates and affects how unwanted proteins are removed.

Condensates · selective autophagy
2026
The EMBO Journal

CaMKII nucleates an osmotic protein supercomplex to induce cellular bleb expansion

A protein assembly can generate local osmotic effects that drive outward protrusions of the cell membrane.

Membrane blebbing · physical mechanisms
2024
Nature Communications

Experimental determination and mathematical modeling of standard shapes of forming autophagosomes

Three-dimensional measurements and physical modeling reveal characteristic shapes formed as autophagosomes grow.

Membrane geometry · mathematical theory
2024
Nature Communications

Single-nucleosome imaging unveils that condensins and nucleosome–nucleosome interactions differentially constrain chromatin to organize mitotic chromosomes

Measurements of individual nucleosomes clarify how condensin activity and contacts within chromatin shape mitotic chromosomes.

Chromatin dynamics · mesoscale simulation
2024
eLife

Syntaxin 17 recruitment to mature autophagosomes is temporally regulated by PI4P accumulation

Experiments and molecular simulations link PI4P accumulation to STX17 membrane insertion and recruitment during autophagosome maturation.

Membrane insertion · autophagosome maturation
07 / Research evolution

One continuous intellectual journey

Moving from physical models of organization toward experimentally testable molecular mechanisms.

Physical models → Molecular mechanisms → Integration with experiments
2016

Physical models

Polymer simulations establish physical models linking chromosome geometry to segregation speed.

2018

Chromosome formation

Mathematical modeling connects chromosome shaping with segregation.

2020

Emergent membranes

Membrane mechanics explains autophagosome shape transitions.

2024

Theory meets data

Quantitative microscopy and simulations connect scales.

2026

Dynamic mechanisms

Membrane turnover, lipid flow and kinetochore architecture.

08 / About

Yuji Sakai
境 祐二

Computational Biophysicist

I am a computational and theoretical biophysicist interested in how living matter self-organizes. Trained in theoretical physics, I use mathematical modeling and molecular dynamics to understand how cells build membranes and establish the physical structures needed for accurate chromosome inheritance.

2024 – PresentProject Associate Professor · Yokohama City University
2022 – 2024Program-Specific Associate Professor · Kyoto University
2017 – 2022Assistant Professor · The University of Tokyo
2012 – 2017Postdoctoral research · RIKEN
Ph.D.Theoretical Physics · Kyushu University
09 / Contact & links

Let’s explore mechanisms together.

For scientific discussions, collaborations and inquiries.