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Intuition alone often fails to decipher the mechanisms underlying the experimental data in Cell Biology and Biophysics, and mathematical modeling has become a critical tool in these fields. However, mathematical modeling is not as widespread as it could be, because experimentalists and modelers often have difficulties communicating with each other, and are not always on the same page about what a model can or should achieve. Here, we present a framework to develop models that increase the understanding of the mechanisms underlying one's favorite biological system. Development of the most insightful models starts with identifying a good biological question in light of what is known and unknown in the field, and determining the proper level of details that are sufficient to address this question. The model should aim not only to explain already available data, but also to make predictions that can be experimentally tested. We hope that both experimentalists and modelers who are driven by mechanistic questions will find these guidelines useful to develop models with maximum impact in their field.

“Essentially, all models are wrong, but some are useful”—a cross-disciplinary agenda for building useful models in cell biology and biophysics