New field of physical bioenergetics studies how cells budget energy

Physical bioenergetics, a new field of study, examines how much energy cells are using and how they apportion that energy. It combines insights from cell biology, energy metabolism and nonequilibrium physics to understand how cells budget energy.

The new field of physical bioenergetics and the challenges it poses are reviewed in a perspective article in the June 17 issue of the Proceedings of the U.S. National Academy of Science.

Although much is known about cell biology and metabolism, the energy costs and constraints of cellular processes are not well known. The authors discuss open questions about cellular energy use and propose an approach to answering these questions by applying theories developed in nonequilibrium physics to cell biology.

Nonequilibrium physics is defined as the study of systems not in thermodynamic equilibrium, a state of balance.

The researchers also note the progress that has been made to date and provide a useful glossary of technical terms and schematics that illustrate the concepts they discuss.

Three main questions are explored:

1) "What are the energy fluxes in cells, and how can they be measured?"

2) "What are the energetic costs of key cellular processes?" 

3) "To what extent do energy fluxes constrain cellular processes?"

Energy flux in cells

The researchers state that detailed information is known about the cell's metabolic pathways that convert environmental energy into forms the cell can use for processing into biomass, or heat, or wastes. But how to measure the energy fluxes in these processes remains unclear, necessitating new techniques.

Some problems noted include measurements of characteristics, such as oxygen consumption or global heat flux, are made on cell populations, not individual cells, so variations are missed.

Also, some methods, such as mass spectrometry, involve destruction of the sample. Thus, a way to measure intracellular fluxes in living cells is needed.

The researchers note that advances using Raman spectroscopy to measure single cell resolution of nutrient uptake may be useful. In general, they state that "techniques to measure energy fluxes with high spatiotemporal resolution are needed."

Energy costs of key cellular processes

"While we have a reasonably good understanding of how cells generate energy through central metabolism, the energetic costs of specific cellular processes are less known," the authors write.

They outline three examples of processes that contribute to the cellular energy budget: "spindle self-organization and chromosome segregation in a mammalian oocyte, protein synthesis in growing cells, and sensory adaptation in chemotactic Escherichia coli."

The challenge, the researchers say, is to measure the energy costs of these processes, which may also reveal other, currently unknown, processes.

The researchers discuss a measuring method called process inhibition, which inhibits one targeted process in the cell, then measures "the change of the global energy flux using respirometry or calorimetry." 

But as they note, the inhibition might change the relationship with other ongoing cellular processes, thus affecting the results. 

The challenge, the authors state, is to understand the "intermediate steps associated with the process of interest, and the coupling between ATP production and ATP consumption." 

ATP is adenosine 5′-triphosphate, the organic compound that supplies the energy to drive many processes in living cells. 

Do energy fluxes constrain cellular processes?

The third question the researchers consider is whether energy fluxes limit or constrain cellular processes.

One example of constraint involves imposing a cell growth rate limit. Another is predicting an upper limit for the efficiency of a molecular motor.

The researchers explain that recent advances in "nonequilibrium dynamics and stochastic thermodynamics have provided tools to study nonequilibrium processes and define physical limits."

Using these tools has made it possible to quantify the use of energy in nonequilibrium processes. The challenge now, they state, is "to apply these theories to cell biology to understand the reciprocal relationship between energy dissipation and cellular functions." 

A new perspective

In conclusion, the researchers reiterate the challenge for both theoreticians and experimentalists in applying existing physical theories to cell biology and developing new experimental testing approaches.

As they summarize: "It boils down to making quantitative predictions using theoretical models and testing them experimentally in cells... Overall, physical bioenergetics provides an opportunity for scientists across disciplines to bring together recent experimental and theoretical advances and address new questions and challenges arising from this new perspective."