Jain Paras, Jolly Mohit Kumar, George Jason T
Department of Bioengineering, Indian Institute of Science, Bangalore 560012.
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843.
bioRxiv. 2025 May 28:2025.05.24.655868. doi: 10.1101/2025.05.24.655868.
Cells invariably encounter unpredictable changes in their microenvironment and undergo adaptation by orchestrating considerable alterations in their molecular states that often result in appreciable phenotypic changes. The timescale of molecular and, therefore, cellular adaptation depends on how quickly the memory of past environmental encounters is lost (and therefore forgotten) by the cell (e.g., degradation rate of proteins unfavorable to the current environment). Here, we study the dynamical implications of two distinct memory mechanisms on cellular responses to a changing environment. The two phenomenological models considered are - 1) Undated memory, wherein each prior environmental exposure has an equal probability to dissipate in the next time step, and 2) Dated memory, wherein each experience is dated and erased according to its order of encounter. We observed that while dated memory leads to faster adaptation in single-step environmental perturbations and helps in quick recovery of cellular benefit, the optimal memory type in the periodic environment depends on the period and cell memory capacity. However, both memory types confer comparable cellular benefits in stochastic environments. We extend the results with these memory types to show how the cost incurred during cellular adaptation (e.g., energetic cost of mRNA and protein production) improves cellular decision-making by delaying the phenotypic response until enough environmental change is experienced by the cells. However, such delayed adaptation proves detrimental to the cells under one-step environmental perturbations. Together, these results elucidate the intricate roles of memory and adaptation cost in phenotypic adaptation in fluctuating environments.
细胞总是会遇到其微环境中不可预测的变化，并通过协调其分子状态的显著改变来进行适应，这些改变往往会导致明显的表型变化。分子以及细胞适应的时间尺度取决于细胞对过去环境遭遇的记忆丧失（并因此被遗忘）的速度有多快（例如，对当前环境不利的蛋白质的降解速率）。在这里，我们研究两种不同记忆机制对细胞对变化环境的反应的动力学影响。所考虑的两种现象学模型是：1）无日期记忆，其中每次先前的环境暴露在下一个时间步长中有相同的概率消散；2）有日期记忆，其中每次经历都有日期，并根据其遭遇顺序被擦除。我们观察到，虽然有日期记忆在单步环境扰动中导致更快的适应，并有助于细胞益处的快速恢复，但在周期性环境中最佳的记忆类型取决于周期和细胞记忆容量。然而，在随机环境中，两种记忆类型赋予细胞的益处相当。我们将这些记忆类型的结果进行扩展，以展示细胞适应过程中产生的成本（例如，mRNA和蛋白质产生的能量成本）如何通过将表型反应延迟到细胞经历足够的环境变化来改善细胞决策。然而，这种延迟适应在单步环境扰动下对细胞证明是有害的。总之，这些结果阐明了记忆和适应成本在波动环境中表型适应中的复杂作用。
