Plastic pollution has become a significant concern in aquatic ecosystems, where photosynthetic microorganisms such as microalgae represent a major point of entry in the food chain. For this reason an important challenge is to better understand the consequences of plastic pollution on microalgae and the mechanisms underlying the interaction between plastic particles and cell's interfaces. In this study, to answer such questions, we developed an interdisciplinary approach to investigate the role of plastic microparticles in the aggregation of a freshwater microalgae species, Chlorella vulgaris. First, the biophysical characterization, using atomic force microscopy, of the synthetic plastic microparticles used showed that they have in fact similar properties than the ones found in the environment, with a rough, irregular and hydrophobic surface, thereby making them a relevant model. Then a combination of optical imaging and separation experiments showed that the presence of plastic particles in microalgae cultures induced the production of exopolysaccharides (EPS) by the cells, responsible for their aggregation. However, cells that were not cultured with plastic particles could also form aggregates when exposed to the particles after culture. To understand this, advanced single-cell force spectroscopy experiments were performed to probe the interactions between cells and plastic microparticles; the results showed that cells could directly interact with plastic particles through hydrophobic interactions. In conclusion, our experimental approach allowed highlighting the two mechanisms by which plastic microparticles trigger cell aggregation; by direct contact or by inducing the production of EPS by the cells. Because these microalgae aggregates containing plastic are then consumed by bigger animals, these results are important to understand the consequences of plastic pollution on a large scale.