The formation of biomolecular condensates by phase separation can be mimicked using fully synthetic, phase-separating DNA-nanomotifs, enabling remarkable control and performance increase in several functional nanomaterials. Stem cells exhibit prominent clusters of macromolecules controlling and executing transcription of genes into RNA, which also form via a phase-separation mechanism. Genes that become transcribed can unfold or even disperse these clusters due to an amphiphilic effect. Here, we deploy amphiphilic DNA-based nanomotifs with a nanomotif-repellent poly-thymine tail to recreate the biologically observed, inducible dispersal for droplets formed from DNA-nanomotifs. We use super-resolution microscopy images of transcriptional clusters in pluripotent zebrafish embryo cells as biological reference data. Time-lapse microscopy, amphiphile titration experiments, and Langevin dynamics simulations demonstrate that the addition of amphiphile-motifs to the synthetic system reproduces the shape changes and dispersal seen for transcriptional clusters in the embryonic cells. Our work illustrates how organization principles of biological model systems can guide the implementation of novel ways to control the mesoscopic organization of synthetic nanomaterials.