While the molecular composition of many cellular segments has been mapped and their structures described, it remains largely unclear how these segments are assembled from individual molecules, and how they are regulated and remodeled to perform distinct cellular functions. Likewise, little is known about how subcellular architecture adapts under stress conditions or how individual cellular compartments communicate to maintain essential physiological processes.

SCALE brings together researchers from biochemistry, cell biology, chemistry, computational biology, informatics, physics, and structural biology to bridge this knowledge gap. The Cluster of Excellence develops innovative experimental approaches—including visual proteomics, super-resolution microscopy, cryo-ET, cryo-EM, time-resolved NMR spectroscopy, optogenetics, and intelligent molecular probes—to simultaneously capture the activity, dynamics, and precise localization of diverse molecular species within cells. At the heart of this effort lies the development of digital twins. Originally established in climate and urban research, digital twins are now being applied by SCALE to the life sciences for the first time. The project develops digital twins of subcellular segments — virtual models that represent molecular structures, dynamics, and interactions with unprecedented spatial and temporal resolution. These models are being designed for various cellular segments, including the bacterial envelope, mitochondrial envelope, neuronal interfaces, nuclear envelope, and the endoplasmic reticulum.

To predict the behavior of these cellular segments at the molecular and cellular levels under conditions of health, stress, and disease, the models integrate experimental data, high-performance computing, and artificial intelligence. The creation of these digital twins follows an iterative process that tightly links experimental and computational approaches:
1. Building data-driven, integrative molecular models
2. Simulating of these structures
3. Experimentally validating predictions to refine and improve the models
Through this recurring cycle, digital twins become increasingly accurate and provide new conceptual frameworks for understanding complex biological processes in an integrated way.

SCALE represents a new generation of science and scientists. By combining state-of-the-art imaging, biochemical analysis, and computational modeling, SCALE drives a paradigm shift from observational to predictive biology. This approach opens new avenues for deciphering molecular mechanisms underlying bacterial resistance, neurodegenerative diseases, and cellular aging, and for translating this knowledge into therapeutic applications.

Beyond research, the developed models will also be used in education and science communication to make complex cellular processes accessible and to train the next generation of scientists. Thus, digital twins will not only become a new standard tool for biological research, but also an innovative medium for communicating science in an open, interactive, and transparent way.
With this integrative vision, SCALE is transforming the way life sciences are conducted – for the benefit of both the scientific community and society.

Involved Institutions:

• Max Planck Institute of Biophysics
• Max Planck Institute for Brain Research
• Frankfurt Institute for Advanced Studies (FIAS)
• Johannes Gutenberg University Mainz
• Saarland University
• European Molecular Biology Laboratory (EMBL), Heidelberg