TMPyP is a porphyrin capable of DNA binding and used in photodynamic therapy and G-quadruplex stabilization. Despite its broad applications, TMPyP’s effect on DNA nanomechanics is unknown. Here we investigated, by manipulating λ-phage DNA with optical tweezers combined with microfluidics in equilibrium and perturbation kinetic experiments, how TMPyP influences DNA nanomechanics across wide ranges of TMPyP concentration (5–5120 nM), mechanical force (0–100 pN), NaCl concentration (0.01–1 M) and pulling rate (0.2–20 μm/s). Complex responses were recorded, for the analysis of which we introduced a simple mathematical model. TMPyP binding, which is a highly dynamic process, leads to dsDNA lengthening and softening. dsDNA stability increased at low (<10 nM) TMPyP concentrations, then decreased progressively upon increasing TMPyP concentration. Overstretch cooperativity decreased, due most likely to mechanical roadblocks of ssDNA-bound TMPyP. TMPyP binding increased ssDNA’s contour length. The addition of NaCl at high (1 M) concentration competed with the TMPyP-evoked nanomechanical changes. Because the largest amplitude of the changes is induced by the pharmacologically relevant TMPyP concentration range, this porphyrin derivative may be used to tune DNA’s structure and properties, hence control the wide array of biomolecular DNA-dependent processes including replication, transcription, condensation and repair.

中文翻译：

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TMPyP 结合在 DNA 中引发复杂、可调节的纳米力学反应


TMPyP 是一种能够结合 DNA 的卟啉，用于光动力疗法和 G-四链体稳定。尽管应用广泛，但 TMPyP 对 DNA 纳米力学的影响尚不清楚。在这里，我们通过在平衡和微扰动力学实验中使用光镊结合微流体操纵 λ 噬菌体 DNA，研究了 TMPyP 如何在广泛的 TMPyP 浓度 (5–5120 nM)、机械力 (0–100 pN)、机械力 (0–100 pN)、 NaCl 浓度 (0.01–1 M) 和牵引速率 (0.2–20 μm/s)。记录了复杂的反应，为了对其进行分析，我们引入了一个简单的数学模型。 TMPyP 结合是一个高度动态的过程，会导致 dsDNA 延长和软化。双链 DNA 稳定性在低 (<10 nM) TMPyP 浓度下增加，然后随着 TMPyP 浓度的增加逐渐下降。过度拉伸协同性下降，很可能是由于 ssDNA 结合的 TMPyP 的机械障碍。 TMPyP 结合增加了 ssDNA 的轮廓长度。添加高浓度 (1 M) 的 NaCl 会与 TMPyP 引起的纳米力学变化竞争。由于最大幅度的变化是由药理学相关的 TMPyP 浓度范围引起的，因此这种卟啉衍生物可用于调节 DNA 的结构和特性，从而控制广泛的生物分子 DNA 依赖性过程，包括复制、转录、缩合和修复。