Decoding transmembrane communication in living cells

April 24th, 2015

Living cells aren’t self-sufficient; they need to interact with their environment in order to survive. But these interactions are extensively controlled by the barrier called the cell membrane, a dynamic entity made up of lipids and proteins. Molecules are constantly passing in and out of the cell through the semi-permeable cell membrane, their movement often orchestrated by different forces and membrane components. This was the level of understanding of this barrier’s structure and function, posited by the ‘fluid mosaic’ model developed by Singer and Nicholson in 1972. Little was known then about minute details of the driving forces at the nano scale.

Until now, the nitty-gritty of how information traverses the membrane had been left to cell biologists’ countless hypotheses. Fast-forward to the 21st century, some of those assumptions have been put to rest by a recent study at NCBS. An interdisciplinary team has used living cells, synthetic lipid analogs and molecular dynamic simulations to understand transbilayer communication between molecules on either side of the bilayered cell membrane. The team consists of cell biologist Satyajit Mayor along with soft matter physicist Madan Rao and their teams at the National Centre for Biological Sciences, Bangalore, and synthetic chemists Ram Viswakarma (IIIM, Jammu) and Zhongwu Guo (Wayne State University, USA).

The team’s studies at the nanoscale have revealed that Phosphatidylserine (PS) is a key component that mediates the communication between the lipids on the inner leaflet, and actin and lipid-anchored proteins on the outer leaflet. PS gets the message across because of the presence of long chain-containing lipids such as those found in ‘solid fats’. That’s how the components on inner and outer leaflets communicate.  These studies show how integral PS is to signalling pathways of the cell, and therefore when absent results in irreparable damage.

“The uniqueness of the study lies in discovering a specific role for PS in nanocluster formation, a building block of ‘lipid rafts’ and how the chemistry of both the outer and inner leaflet facilitate this process. For this we have adopted an array of methods which combines biology, genetics, chemistry and physics to provide an explanation for the formation of nanoclusters” says Anupama Ambika Anilkumar, one of the first authors of the paper published online on 23 April, 2015, in the journal Cell.

Lipid rafts are microenvironments in the membrane made up of clusters of lipids and protein receptors, and are involved in molecule trafficking and assembly. Refuting early theories on the random combination of lipids to construct these lipid rafts, this study shows that the formation of these “nanoclusters” of lipids is an active process templated by the actin cytoskeleton on the inner leaflet. This understanding also points to further clues about the role of these clusters. They have been hypothesized to function as a ‘sorting station’ for components to be recruited for signalling events on the cell surface.

The discovery of PS as a vital component in the transmembrane communication would advance our understanding of the cell membrane’s microenvironment. It would also help scientists understand how these nanoclusters function and what proteins are involved in their assembly. Additional experiments in Mayor’s lab are underway to draw the complete picture of the cell’s communications and the anchors of the PS species. These entities also play an important role in various other cell functions and are hence important problems to pursue.

“There is no earlier evidence of how these clusters are formed by lipidic interactions. My colleague and co-first author, Riya Raghupathy established methods to assay the role of long-acyl chain lipid species, and along with Parvinder Pal Singh, developed the synthetic analogues used in this study. Anirban Polley, working with Madan, conducted molecular dynamic simulations; both of these are an integral part of this study and I am grateful for having such terrific collaborators,” said Anupama Anilkumar.

Decrypting this communication could help explain how signals are both read and interpreted by the cell, with implications for a number of diseases caused by alteration in lipid balance or composition. Understanding how these lipids, the “gatekeepers” of the cell, function might also help deter the progression of viral diseases, by potentially disrupting the interaction of membrane components with the viruses.

The paper can be accessed at:
http://dx.doi.org/10.1016/j.cell.2015.03.048

Conservation perceptions

July 2015

India, being rich in its biodiversity, needs to make space for both its ever growing human population as well as its wildlife to live in harmony within the limited supply of resources. Most of the laws and policies related to efficient utilisation of these resources for the sustenance of both population is decided primarily with the help of experts from the fields of ecology, conservation and environment. For the first time, a group of ecologists, environmental and conservation scientists, took a step in reaching out to the general public for their opinions and concerns. A nation-wide survey was conducted consisting of 572 respondents mostly from the educated, urban and sub-urban population who were asked to list up to 10 most important questions that need to be addressed for better management and conservation of biodiversity in the country. The final outcome of this large scale assessment has been summarised into a list of 152 questions spread across 17 broad themes. Within the high ranking topics of concerns were ‘Policy and Governance’, ‘Biodiversity and Endangered species’ and ‘Protection and Conservation’.

In previous surveys, mostly the experts or practitioners had taken part while this survey uniquely involves a whole wider population. The authors believed that a wider representation would help in highlighting the important issues as per the public and also help them avoid biases that experts tend to develop as a result of their knowledge in their respective fields of expertise. The involvement of people from various parts of the country also helped in identifying the emergent problems in the local contexts.

There is a pressing need to understand the changes in the environment and what drives the changes in it. The survey highlights the priority issues which can be used as a guiding framework for conservation practitioners, researchers, citizens, policy makers and funders to direct their effort’s in India’s conservation landscape. Many issues identified as a result of this survey are relevant at a global scale while there are many others that are of importance at smaller scales (country, region etc). Thus the region specific assessment helps in looking at customised solutions for the local conditions. Dr. Varun Varma, first author of the paper, said “our analysis reveals themes with lower than average emphasis compared to other studies, such as – marine ecosystems, ecosystem function and services. The lack of emphasis is suggestive of lower awareness and/or press coverage of issues within these themes.”

Most of the respondents of the survey was limited to the literate section of the urban areas. Subsequent surveys could use more resources like the print media, and manpower in order to be more inclusive of the participants. Usage of vernacular languages could help reaching out to the rural population also. Nevertheless the present study was a huge leap in widening the representative class of citizens in the environmental and ecological issues in the Indian context. People are an integral part of the conservation of biodiversity and ecosystems. Their active participation helps policy makers and scientists make better decisions.