该文发表于2026年2月18日，探讨细胞生物学如何受物理学限制，呼应 Erwin Schrödinger 在1944年提出的论点：生命必须遵守物理定律。研究人员描述了真核细胞细胞质内拥挤度的「刚刚好」区间：拥挤太少会降低分子之间具生产性的相遇，拥挤太多则会使分子难以移动，并损害代谢、蛋白质合成、生长与分裂等核心功能。早期证据（包括1980年代的青蛙卵细胞质实验）显示，即使是轻微稀释也可能使有丝分裂与 DNA 复制停止。

核心的量化框架指出，像核糖体这类大型巨分子通常约占细胞质溶胶中已溶解巨分子体积的30%到40%，这暗示演化已将细胞调校在接近狭窄运作最佳点的位置。为了直接测量介尺度拥挤，Liam Holt 在2010年代中期引入了基因编码的多聚奈米粒子（GEMs）：可发萤光的球形蛋白质追踪粒子，直径约40奈米（原文：40 nanometers），尺寸与核糖体相近。2018年，对培养酵母与人类细胞中 GEM 运动的追踪显示，细胞质拥挤度会随营养条件改变，表示拥挤是动态调控而非固定不变。

机制上的关键线索是 mTORC1，这个真核生物主要的营养感测器与生长调节器会调节核糖体生成，进而改变细胞质的物理密度。当 mTORC1 受到化学抑制时，核糖体浓度下降而 GEM 扩散增加，将营养讯号与细胞内运输性质连结起来。其关键意涵是一种生物物理学上的刀锋平衡：细胞必须耗能以维持流动性与反应频率，同时避免拥挤不足与过度拥挤，而这些发现也挑战了在高度拥挤细胞环境中反应伙伴如何彼此找到对方的简化假设。

Published on February 18, 2026, the article examines how cell biology is constrained by physics, echoing Erwin Schrödinger’s 1944 argument that life must obey physical laws. Researchers describe a Goldilocks regime of intracellular crowding in eukaryotic cytoplasm: too little crowding reduces productive molecular encounters, while too much immobilizes molecules and impairs core functions such as metabolism, protein synthesis, growth, and division. Early evidence, including 1980s frog egg cytoplasm experiments, showed that even slight dilution could halt mitosis and DNA replication.

A central quantitative framing is that large macromolecules such as ribosomes typically account for about 30% to 40% of dissolved macromolecular volume in cytosol, suggesting evolution has tuned cells near a narrow operating optimum. To directly measure mesoscale crowding, Liam Holt introduced genetically encoded multimeric nanoparticles (GEMs) in the mid-2010s: fluorescent spherical protein tracers approximately 40 nanometers (original: 40 nanometers) in diameter, similar in size to ribosomes. In 2018, tracking GEM motion in cultured yeast and human cells showed that cytoplasmic crowding shifts with nutritional conditions, indicating crowding is dynamically regulated rather than fixed.

The mechanistic lead is mTORC1, the major eukaryotic nutrient sensor and growth regulator, which modulates ribosome production and thus the physical density of the cytoplasm. When mTORC1 was chemically suppressed, ribosome concentration fell and GEM diffusion increased, linking nutrient signaling to intracellular transport properties. The key implication is a biophysical knife-edge: cells must spend energy to maintain fluidity and reaction frequency while avoiding both undercrowding and overcrowding, and the findings challenge simple assumptions about how reactive partners find each other in highly packed cellular environments.